Abstract: Registered nurses (RN) coordinate acute mental health units on a 24-hour basis and it behoves researchers to actually ask these nurses what they think contributes to their ability to work with patients in optimistic ways. In this study, 40 RN working in acute mental health settings were asked a series of questions to explore positive aspects of nursing work, which includes therapeutic optimism. Three themes were identified: (i) different ways nurses foster therapeutic optimism; (ii) perceptions of how an optimistic environment is fostered, and (iii) improvement of ward culture. Findings show the pivotal role mental health nurses have in improving teamwork, good communication, sharing, and collaboration, in addition to preceptoring and supervision. Furthermore, effective clinical management is essential to therapeutic optimism and, in this research, is considered to be the aspect of acute mental health nursing most relevant to improving the ward culture.
Abstract: Mental health nurses work with acutely unwell patients, and the busy setting is characterised by unpredictable events. This paper is a report of a review conducted to identify, analyse and synthesize research in adult acute inpatient mental health units, which focused on nurse-patient interaction. Several electronic databases were searched using relevant keywords to identify studies published from 1999-present. Qualitative studies published in English were included if they specifically investigated nurse-patient interaction in acute inpatient care in adult settings. Eighteen studies were included (23 papers). Findings were grouped into the following six categories: 1) sophisticated communication; 2) subtle discriminations; 3) managing security parameters; 4) ordinary communication; 5) reliance on colleagues; and 6) personal characteristics. These studies of acute inpatient mental health units reveal that nurse communication involves interpersonal approaches and modalities that exemplify highly developed communication and personal skills designed specifically for this challenging setting. Further quality research should focus on the conditions that enable the development of therapeutic interactional skills and the relationship of these skills to the nuanced context in which they are practiced.
Abstract: The regional expression of the transcription factors c-Fos and FosB/ΔFosB was examined in rats given acute exposure to intravenous methamphetamine (METH) or repeated intravenous METH self-administration. One group of rats self-administered METH via lever pressing in 2 h sessions every day for 3 weeks and on a final test day received self-administered METH as usual. A second group with the same METH self-administration history received saline infusions on the test day, to induce drug-seeking behavior. Other rats were trained with infusions of intravenous saline that were yoked to the passive delivery of METH in the other two groups. On test day, half of these yoked rats received passive METH infusions for the first time, whereas the others received saline as usual. The results showed that acute METH produced a characteristic signature of Fos expression with elevations in striatal, cortical, and extended amygdala regions. Importantly, rats with a 3-week history of METH self-administration displayed similar regional Fos expression to rats receiving METH for the first time. Rats seeking, but not receiving, METH on the test day had augmented Fos in the lateral hypothalamus, septum, and vertical limb of the diagonal band of Broca, suggesting a primary role for these regions in METH-seeking behavior. Both acute and chronic METH activated orexin-positive cells in the perifornical area of the hypothalamus. FosB/ΔFosB was elevated in the lateral hypothalamus, posterior ventral tegmental area, central amygdala, and dorsal raphe of all the rats with a history of METH self-administration. This occurred regardless of whether they received METH on test day, suggesting presence of the long-lived FosB isoform, ΔFosB. Overall, these results show persistent upregulated regional brain Fos and FosB/ΔFosB expression with chronic METH self-administration and indicate a role for the lateral hypothalamus and lateral septum in METH-seeking behavior.
Abstract: The effects of Δâ¹-tetrahydrocannabinol (Δâ¹-THC; 0.3, 1, 3 and 10 mg/kg), and the fatty acid amide hydrolysis inhibitor URB-597 (0.1 and 0.3 mg/kg), on auditory and olfactory go/no-go discrimination tasks were examined in rats. The aims were to assess (i) whether simple olfactory and auditory discrimination tasks are sensitive to cannabinoid interference and (ii) whether manipulation of endogenous cannabinoid levels with URB-597 might have adverse effects on perceptual and cognitive functions. Thirsty rats were trained to nose poke at a 'sniff port', where odours were briefly presented. After one odour (S+, lemon), licks made at an adjacent tube were rewarded with water, whereas licks after a second odour (S-, strawberry) were unrewarded. In an analogous auditory task, nose pokes produced an auditory S+ (beep) or S- (white noise). Δâ¹-THC and URB-597 impaired performance on the auditory but not the olfactory discrimination task. Auditory performance was still affected on the day after Δâ¹-THC (3 and 10 mg/kg) and URB-597 (0.3 mg/kg) exposure. Δâ¹-THC and URB-597 markedly impaired olfactory discrimination reversals without disrupting acquisition of the original discrimination. Rimonabant (CB1 antagonist; 3 mg/kg) reversed all Δâ¹-THC and URB-597 effects on auditory discriminations and olfactory discrimination reversals. These results confirm impairment of cognitive flexibility (reversal learning) by cannabinoids and show remarkable sensitivity of auditory discrimination performance to Δâ¹-THC and the augmented endocannabinoid signalling produced by URB-597.
Abstract: The popular party drug MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") increases sociability in both humans and laboratory animals. Recent research suggests that these prosocial effects may involve serotonin (5-HT)-stimulated hypothalamic release of the neuropeptide oxytocin. WAY 100635, a 5-HT(1A) receptor antagonist, prevents MDMA-induced increases in plasma oxytocin and also reduces MDMA-mediated increases in social interaction in rats. The present study used c-Fos immunohistochemistry to determine the possible role of 5-HT(1A) receptors in MDMA-mediated activation of oxytocin synthesizing neurons. Male Wistar rats (n=8/group) were administered MDMA (10mg/kg, i.p.) with or without WAY 100635 (1mg/kg, i.p.) pre-treatment and c-Fos expression was then assessed throughout the brain. MDMA significantly increased locomotor activity and this effect was partly prevented by WAY 100635, in agreement with previous studies. WAY 100635 significantly reduced MDMA-induced c-Fos expression in a subset of brain regions examined. A particularly prominent reduction was seen in the oxytocin-positive neurons of the supraoptic nucleus and paraventricular hypothalamus, with more modest reductions in the Islands of Calleja, median preoptic nucleus, somatosensory cortex and nucleus of the solitary tract. WAY 100635 did not alter MDMA-induced c-Fos expression in the striatum, thalamus, or central amygdala. These results indicate that MDMA's action on oxytocin producing cells in the hypothalamus is mediated through 5-HT(1A) receptors and that certain specific cortical, limbic and brainstem sites are also activated by MDMA via these receptors.
Abstract: This article synthesises principles and ideas from relevant literature on professional boundaries and applies them to higher education settings with the intention of contributing to contemporary debates on appropriate, respectful, and ethical conduct in academia. This is against a background of structural changes and growing complexity of academic institutions in concert with decreasing adherence to rules of conduct and established privileges historically handed down from traditional universities. The professional and personal conduct of nurse academics is increasingly unfettered in association with 'market' forces and simultaneously more available for scrutiny in association with a greater awareness of and institutionalisation of human rights and protections across all sectors of society.
Abstract: Developing a researchable question or quality improvement project from a broad clinical problem is a key challenge for mental health nurses. In this paper, we provide an overview of some of the steps involved in proceeding from an initial ?problem? within a clinical setting to determining a research question with clear conceptual components that leads to appropriate methods to explore the topic or answer the question. The focus of the proposed quality or research study must be clear to clinicians and potential participants and meet professional responsibilities. Conducting high quality research and quality initiatives will likely improve care and outcomes for mental health consumers as well as providing a reliable evidence-based foundation for further improvements.
Abstract: The aim of this paper is to discuss issues impacting on consumer workforce participation and challenges that continue to arise for these workers, other service providers, and the mental health system. The literature identifies the following issues as problematic: role confusion and role strain; lack of support, training, and supervision structures; job titles that do not reflect actual work; poor and inconsistent pay; overwork; limited professional development; insufficient organizational adaptation to expedite consumer participation; staff discrimination and stigma; dual relationships; and the need to further evaluate consumer workforce contributions. These factors adversely impact on the emotional well-being of the consumer workforce and might deprive them of the support required for the consumer participation roles to impact on service delivery. The attitudes of mental health professionals have been identified as a significant obstacle to the enhancement of consumer participation and consumer workforce roles, particularly in public mental health services. A more comprehensive understanding of consumer workforce roles, their benefits, and the obstacles to their success should become integral to the education and training provided to the mental health nursing workforce of the future to contribute to the development of a more supportive working environment to facilitate the development of effective consumer roles.
Abstract: Comparisons were made between young (3-6 months) and aged (20-30 months) Wistar rats on locomotor activity, emergence, social interaction and cat odor avoidance. Aged rats were less active and spent less time in the open field during the emergence test than younger rats. Older rats also showed fewer contacts with a novel conspecific in the social interaction test, although total duration of interaction did not differ. There were very few behavioral differences between male and female rats. Older rats were less reactive than younger rats in a test of cat odor avoidance. However, they expressed similar amounts of cat odor-induced Fos in the posterior accessory olfactory bulb, a critical region for processing the predator odor stimulus. Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus. These results indicate that aged rats are less reactive than younger rats to predator odors due to decreased responsiveness in defense-related but not necessarily olfactory circuits.
Abstract: Aims and objectives.  To determine clinical mental health nurses' views and preferences about continuing professional development. Background.  Participation in continuing professional development is now expected for nurse and midwifery registration. However, it is unclear how clinically based mental health nurses view continuing professional development and its relevance to career intentions. Design.  Qualitative. Method.  Semi-structured face-to-face interviews with mental health nurses (n = 50) drawn from inpatient mental health units. Results.  The most prominent factor identified through this research is that the majority of the fifty participants valued continuing professional development and sought more opportunities to participate. They particularly favoured in-house locally based sessions targeting patient-related clinical skills enhancement. Importantly, this interest in continuing professional development was not confined to new graduates needing to consolidate their skills. Work-based flexibility, the types of courses available and opportunities for study leave were also identified as important factors. Of the 50 nurses interviewed, 40% expressed a desire for continuing professional development vis-à -vis remaining in the service; 30% of nurses responded to the same question with an emphasis on the importance of collegial support amongst peers and management; and 30% of the nurses indicated their primary focus for continuing professional development was to further their tertiary studies. Conclusions.  These results are not only timely given the requirements around continuing professional development, but are also important to drive improvements in quality continuing professional development where needs are prioritised, discussed and agreed on. Relevance to clinical practice.  Findings from this study highlight the value clinical nurses place on having access to work-based and clinically focussed education and development. Relevant on-the-job professional education has the potential to improve job satisfaction and retention of clinical nurses, thus ultimately directly and positively influence patient care.
Abstract: Acute inpatient mental health units are busy and sometimes chaotic settings, with high bed occupancy rates. These settings include acutely unwell patients, busy staff, and a milieu characterised by unpredictable interactions and events. This paper is a report of a literature review conducted to identify, analyse, and synthesize ethnographic research in adult acute inpatient mental health units. Several electronic databases were searched using relevant keywords to identify studies published from 1990-present. Additional searches were conducted using reference lists. Ethnographic studies published in English were included if they investigated acute inpatient care in adult settings. Papers were excluded if the unit under study was not exclusively for patients in the acute phase of their mental illness, or where the original study was not fully ethnographic. Ten research studies meeting our criteria were found (21 papers). Findings were grouped into the following overarching categories: (1) Micro-skills; (2) Collectivity; (3) Pragmatism; and (4) Reframing of nursing activities. The results of this ethnographic review reveal the complexity, patient-orientation, and productivity of some nursing interventions that may not have been observed or understood without the use of this research method. Additional quality research should focus on redefining clinical priorities and philosophies to ensure everyday care is aligned constructively with the expectations of stakeholders and is consistent with policy and the realities of the organisational setting. We have more to learn from each other with regard to the effective nursing care of inpatients who are acutely disturbed.
Abstract: Each nurse educator's pedagogy underpins their understanding of and approach to teaching and learning, regardless of whether this has been reflected upon or articulated. In this paper, we overview factors and issues that should be considered when developing a teaching philosophy of nursing education and set out broad differences between traditional and contemporary pedagogic models and various ways of knowing. As values underpin any teaching framework these are considered in relation to pedagogies, epistemologies and their relevance to nursing practice. Key teacher roles and strategies that are congruent with a contemporary pedagogy for teaching nursing in the classroom or the clinical setting are also outlined. A premise for writing this paper was that clarifying one's own understandings of education and knowledge and the implicit values held within those terms and processes will contribute to greater self-awareness and more effective teaching of nursing. Education approaches underpinned by a sound teaching philosophy and framework can facilitate an educationally sound and positive experience for learners.
Abstract: ACCESSIBLE SUMMARY: •  This study collected a snapshot of current handover practice in mental health settings from doctors, nurses, community and allied health staff. The handover of care is a very important process as breakdown in communication during shift changes or when a patient is transferred from one place to another is one of the leading causes of adverse events and failure of care or services. •  Structuring the content of the verbal component of handover and documenting the handover may make measurable improvements to the effectiveness of clinical handovers. •  Sometimes negative statements are expressed about a patient during handover. This should be avoided as negative labelling and judgement of a patient or illness can have serious consequences for patient care, especially when this information, if passed on, could prejudice the oncoming shift. •  The inclusion of prompts or simulation models to recognize and escalate patients that are deteriorating in their physical condition or mental state may improve patient outcomes by prompting action to avert adverse events. ABSTRACT: This study collected an area-wide snapshot of current handover practice in psychiatric settings which included acute care units and community mental health centres. The study was conducted in two stages. Firstly, a questionnaire was sent to all clinical mental health staff within an area-wide health service regarding normal handover procedures and processes. The second part of the study used non-participant observers to evaluate actual handovers in inpatient and community settings. Of the 1125 surveys distributed in stage one, 380 (34%) were returned completed. Of the 40 handovers observed in stage two in which 637 patients were discussed, 40% included at least one consultant psychiatrist or registrar as a participant. Almost all the handovers were completed face-to-face in a specific location with a set time and duration. Eighty-six per cent of respondents reported that deteriorating patients were escalated for rapid response. The results of the survey and structured observations support the issues emerging from the literature from medical, surgical and clinical team handovers. Additionally, the issue of identifiers for deterioration of a psychiatric patient emerged as an area worthy of further investigation and incorporation into clinical handover education and training for psychiatric services.
Abstract: The aim of this study was to determine what patient characteristics are used to decide whether a patient is or is not admitted to a psychiatric hospital, and what happens to those not admitted. A further aim was to determine if high levels of risk on admission predict seclusions, length of stay, or readmission within 28 days. Data were collected prospectively on consecutive presentations to an admission office via case notes and electronic databases. Eighty percent (100/127) of the adults presenting to the admission office over a typical month were admitted to hospital. Patients were more likely to be admitted if they were experiencing psychosis or exacerbation of schizophrenia, referred by other doctors or mental health teams, had a legal reason for referral, or if they were homeless. There was no association between risk for violence or suicide and seclusion rates, length of stay, or being readmitted within 28 days. It was reassuring to find that 85% of those not admitted were referred to other mental health providers, and none required admission over the following month. This study found high rates of seclusion and readmissions within 1 year, which requires further study to find strategies to reduce these rates.
Abstract: Accumulating evidence indicates that the neuropeptide oxytocin (OXY) may modulate reward-related behavioural responses to methamphetamine (METH) administration. Limited research has examined the effect of OXY on METH-induced conditioned place preference (CPP) and little is known about the neural mechanisms involved. A Fos immunohistochemistry study recently demonstrated that peripheral OXY administration reduced METH-induced Fos expression within the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in rats. The current study aimed to (i) investigate the effect of systemically administered OXY on METH-induced CPP, (ii) determine the effectiveness of a single-trial CPP procedure with METH, in order to (iii) evaluate whether pretreatment with OXY injected directly into the NAc core or the STh attenuates METH-induced CPP. Results showed that male Sprague Dawley rats learned to associate unique compartmental cues with METH (1mg/kg, i.p.) such that they spent more time in the METH-paired compartment and less time in the saline-paired compartment. Pretreatment with systemic OXY (0.6mg, i.p.), or OXY (0.6ng, i.c.) microinjected into the NAc core or the STh prior to METH administration attenuated the formation of a CPP to METH. This provides further evidence that OXY acts within either the NAc core or the STh to reduce the rewarding effects of METH administration.
Abstract: Undergraduate nurses are employed as assistants in nursing (AIN) in inpatient mental health settings; however, there is a paucity of published research exploring registered nurses' (RN) views about the AIN role in these settings. This qualitative study documents the views and experiences of RN working with undergraduate AIN. Fifty structured face-to-face interviews were analysed, and the results are discussed in three sections. The first section outlines RN perceptions of qualities and skills required of AIN in mental health, and the responses primarily focus on communication skills, initiative, and willingness to learn. The second section targets factors in the workplace that might enhance the interest of AIN in a mental health nursing career; the responses emphasize their need to work with experienced staff. The last section outlines RN expectations of AIN, most of which are met and involve physical observations and technical tasks; less fulfilled activities primarily cluster around interactions with patients. Findings highlight the advantages and disadvantages of drawing on undergraduate nursing students as AIN in mental health settings. Communication skills, personal initiative, safety training to prevent violence, and education to increase knowledge and awareness about mental illness, diagnosis, and mental status-related skills were all important concerns articulated by RN.
Abstract: Interestingly, there are very few guidelines in the literature to assist novice nurse PhD examiners. In this paper, we aim to provide information to nurses, researchers or early career academics who have little experience in assessing a university thesis. The article provides background information about recent changes in the university sector; overviews some research on experienced examiners views; presents factors that differentiate between high and low quality PhD theses; and outlines some pointers that may be useful when marking at the doctoral level.
Abstract: Mephedrone (4-methylmethcathinone) is a novel recreational drug that has rapidly increased in popularity in recent years. Users report mephedrone as having the stimulant-like qualities of methamphetamine and cocaine, combined with the prosocial, entactogenic effects of 3,4-methylenedioxymethamphetamine (MDMA). Anecdotal and case study reports indicate that mephedrone may have the potential to engender compulsive patterns of use as well as toxicity in overdose. However, there have been almost no neuropharmacological investigations of the drug up to this point. Here we examined the effects of two different mephedrone doses [15 and 30 mg/kg, intraperitoneal (IP)] relative to the well-known stimulant methamphetamine (2 mg/kg IP) in adolescent rats. Rats were injected, assessed for locomotor activity for 60 minutes and then tested in a 10-minute social preference test (measuring time spent in close proximity to a real rat versus a dummy rat). Their brains were then processed using Fos immunohistochemistry to determine patterns of brain activation. Results showed that mephedrone caused profound locomotor hyperactivity at both dose levels while tending to reduce social preference. Patterns of Fos expression with mephedrone resembled a combination of those observed with methamphetamine and MDMA, with particularly strong Fos expression in the cortex, dorsal and ventral striatum, ventral tegmental area (typical of both MDMA and methamphetamine) and supraoptic nucleus (typical of MDMA). These results demonstrate for the first time the powerful stimulant effects of mephedrone in animal models and its capacity to activate mesolimbic regions. These results also provide some empirical basis to user reports that mephedrone subjectively resembles a MDMA/methamphetamine hybrid.
Abstract: There is considerable evidence suggesting genetic factors play an important role in the pathophysiology of depression, possibly by increasing susceptibility to repeated environmental stressors. Recent linkage studies have associated a polymorphism of the gene coding for the P2X7 receptor (P2X7R) with both major depressive disorder and bipolar disorder. Here we assessed whether P2X7 deletion affected the behavioural and neural response to repeated stress. P2X7R knockout (P2X7(-/-)) mice were subjected to the forced swim test for three consecutive days and neuronal activation in response to the third exposure was assessed using c-Fos immunohistochemistry. In addition, anxiety was evaluated in another group of P2X7(-/-) mice using the elevated plus maze (EPM) and light dark emergence (LDE) tests. Equivalent levels of immobility were observed in P2X7(-/-) mice and wild-type (WT) mice on the first exposure to forced swim, but much greater immobility was seen in WT mice on second and third exposures. This suggests that P2X7(-/-) mice exhibit an impaired adaptive coping response to repeated stress. Reinforcing this view, c-Fos expression in the dentate gyrus of the hippocampus and in the basolateral amygdala was seen in WT mice but not P2X7(-/-) mice following repeated forced swim. In addition, decreased locomotor activity was detected in P2X7(-/-) mice without any specific effects on anxiety in the LDE test. However, P2X7(-/-) mice showed greater anxiety-like behaviour in the EPM. These data suggest that the P2X7R may be involved in the adaptive mechanisms elicited by exposure to repeated environmental stressors that leads to the development of depression-like behaviours. This suggests that P2X7R antagonists may be useful therapeutics for the treatment of major depression, possibly by increasing resilience in the face of repeated stress.
Abstract: In this article, we identify key aspects for enhancing real-world research in mental health care clinical settings and broadly discuss some practicalities and issues that must be considered beforehand.
Abstract: Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.
Abstract: Cannabis increases the risk of schizophrenia in genetically vulnerable individuals. In this study we aim to show that the schizophrenia susceptibility gene neuregulin 1 (Nrg1) modulates the development of tolerance to cannabinoids in mice. Nrg1 heterozygous (HET) and wild-type (WT) mice were treated daily for 15 d with the synthetic analogue of Delta9-tetrahydrocannabinol, CP55,940 (0.4 mg/kg). We measured the impact of this exposure on locomotor activity, anxiety, prepulse inhibition (PPI), body temperature and FosB/DeltaFosB immunohistochemistry. Tolerance to CP55,940-induced hypothermia and locomotor suppression developed more rapidly in Nrg1 HET mice than WT mice. Conversely in the light-dark test, while tolerance to the anxiogenic effect of CP55,940 developed in WT mice over days of testing, Nrg1 hypomorphs maintained marked anxiety even after 15 d of treatment. Repeated cannabinoid exposure selectively increased FosB/DeltaFosB expression in the lateral septum, ventral part (LSV) of Nrg1 HET but not WT mice. On day 1 of exposure opposite effects of CP55,940 treatment were observed on PPI, i.e. it was facilitated in Nrg1 hypomorphs and impaired in WT mice, despite the drug significantly impairing the acoustic startle reflex equally in both genotypes. These effects of CP55,940 on PPI were not maintained as both genotypes became tolerant to cannabinoid action with repeated exposure. Our results highlight that Nrg1 modulates the development of cannabinoid tolerance dependent on the parameter being measured. Furthermore, these data reinforce the notion that the VLS is an important brain region involved in Nrg1-cannabinoid interactions.
Abstract: PURPOSE.  An overview of approaches used in contemporary mental health research to consider when coordinating research agendas is presented. Connections between the research-practice gap and evidence-based practice are explored. Collaboration, as a key concept and practice, is investigated particularly in relation to community and consumer participation in mental health research. CONCLUSIONS.  Non-commensurate belief systems, inadequate infrastructure, and institutional tendencies maintain the status quo and constitute significant impediments to widespread planned and integrated research programs. PRACTICE IMPLICATIONS.  Communication and trust building between researchers and practitioners is central to developing effective collaborations that can deliver more effective health care.
Abstract: In acute inpatient mental health services, patients commonly demonstrate extreme behaviours. A number of coercive practices, such as locked doors, enforced medication and seclusion, are used in these settings to control such behaviours. The aim of this report is to explore briefly some of the contemporary debates pertaining to seclusion. A perusal of the literature reveals a clarion call to end the practice of seclusion, without consideration of feasible alternatives. It is hoped that this brief report will encourage further evidence-based discussion and research initiatives on this important ethical topic.
Abstract: There is considerable debate on the use and abuse of journal impact factors and on selecting the most appropriate indicator to assess research outcome for an individual or group of scientists. Internet searches using Web of Science and Scopus were conducted to retrieve citation data for an individual in order to calculate nine variants of Hirsch's h-index. Citations to articles published in a wide range of psychiatric journals in the periods 1995-99 and 2000-05 were analyzed using Web of Science. Comparisons were made between journal impact factor, h-index of citations from publication to 2008, and the proportion of articles cited at least 30 or 50 times. For up to 14 years post-publication, there was a strong positive relationship between journal impact factor and h-index for citations received. Journal impact factor was also compared to the percentage of articles cited at least 30 or 50 times-a comparison that showed wide variations between journals with similar impact factors. This study found that 40%-50% of the articles published in the top ten psychiatry journals ranked by impact factor acquire 30 to 50 citations within ten to fifteen years. Despite certain flaws and weaknesses, the h-index provides a better way to assess long-term performance of articles or authors than using a journal's impact factor, and it provides an alternative way to assess a journal's long-term ranking.
Abstract: For this quantitative study, a cross-sectional design was used to assess patients' ratings regarding receiving difficult news pertaining to their psychiatric illness, such as deleterious lifestyle consequences and lifelong medications. One hundred inpatients were interviewed and completed the survey. Nearly all agreed they had a legal or moral right to information about their diagnosis, and most agreed they should be told their diagnosis. The majority believed the doctor was the best person to tell them their diagnosis, and more than half indicated that not providing a diagnosis was more concerning than be ing told. Approximately two fifths of patients indicated they would prefer to hear difficult news in the presence of key family members or over several sessions, and more than three quarters thought providing hope, regardless of circumstances, was important. The highest response rates were for staff to provide accurate and reliable information, be honest and answer patients' questions, and inform patients of their treatment options and side effects. These results indicate the importance of communicating accurate and timely information to patients in an empathic and understanding manner.
Abstract: Increasingly, nurses are expected to undertake activities to demonstrate community engagement as part of their continuing professional development. Such collaborative education activities can be mutually beneficial and stimulating, and when goals are aligned, valuable outcomes can be produced.
Abstract: OBJECTIVE: We aimed to describe medication side effects in a cross-section of young people taking low-dose risperidone, using a self-report measure. METHODS: The Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) was completed by 66 patients aged between 6 and 18 years who had been taking low-dose risperidone (alone or in conjunction with other medications) for up to 13 years. RESULTS: Young persons, overall, seemed to tolerate risperidone well, but longer exposure to the medication was associated with higher side effect levels, particularly for the psychic (pertaining to mind and emotion) and extrapyramidal subscales. The most common complaints related to psychic side effects, such as tiredness, difficulty concentrating, difficulty remembering things and increased dreaming. CONCLUSIONS: Clinicians need to monitor the side effects of young patients taking low doses of risperidone, and other psychotropics, and maintain vigilance in those who have been taking medication for extended periods.
Abstract: 3,4-Methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in hippocampal protein expression measured 8 weeks after chronic administration of GHB (500mg/kg), MDMA (5mg/kg) or their combination (GHB/MDMA). The drugs were administered once a day for 10 days in an environment with an elevated ambient temperature of 28 degrees C. Results showed significant changes in protein expression, relative to controls, in all three groups: MDMA and GHB given alone caused residual changes in 8 and 5 proteins respectively, while the GHB/MDMA combination significantly changed 6 proteins. The altered proteins had roles in neuroplasticity, neuroprotection, intracellular signalling and cytoskeletal function. The largest change (-4.3-fold) was seen in the MDMA group with the protein C-crk: a protein implicated in learning-related neuroplasticity. The second largest change (3.0-fold) was seen in the GHB group in Glutathione-S-transferase (GST), a protein that protects against oxidative stress. Two cytoskeletal proteins (Tubulin Folding Cofactor B and Tropomyosin-alpha-3 chain) and one plasticity related protein (Neuronal Pentraxin-1 NP1) were similarly changed in both the MDMA and the GHB groups, while two intracellular signalling proteins (alpha-soluble NSF-attachment protein and subunits of the V-type proton ATPase) were changed in both the MDMA/GHB and the MDMA groups. These results provide some insight into the molecular pathways possibly underlying the lasting cognitive deficits arising from GHB and/or MDMA use.
Abstract: There is a growing expectation for staff to participate in benchmarking activities. If benchmarking projects are to be successful, managers and clinicians need to be aware of the steps involved. In this article, we identify key aspects of benchmarking and consider how clinicians and managers can respond to and meet contemporary requirements for the development of sound benchmarking relationships. Practicalities and issues that must be considered by benchmarking teams are also outlined. Before commencing a benchmarking project, ground rules and benchmarking agreements must be developed and ratified. An understandable benchmarking framework is required: one that is sufficiently robust for clinicians to engage in benchmarking activities and convince others that benchmarking has taken place. There is a need to build the capacity of clinicians in relation to benchmarking.
Abstract: Acute inpatient mental health units can be seen as one important link in the chain of complementary mental health specific and generic community support services that need to address the real needs of people in the area from which clients are drawn. This article reviews the reasons for admission to these units and research initiatives to evaluate alternative models of care within the community. Assertive community treatment and other alternative programs are discussed within a continuum of community-psychiatric support intervention models. An argument is then developed for mental health systems to be conceived within a continuous care framework for all service users, and with recovery in the forefront of service design and delivery. Further research is required to define nursing clinical priorities and philosophies to ensure a recovery focus in which care is aligned with that of consumer expectations and is consistent with other service providers.
Abstract: There is emerging evidence that the neuropeptide oxytocin may be utilised as a treatment for various psychopathologies, including drug addictions. Here we used an animal model to assess whether oxytocin might be effective in the treatment of methamphetamine addiction. Sprague-Dawley rats were trained to lever press to intravenously self-administer methamphetamine under a progressive ratio schedule of reinforcement. Once responding had stabilised, one group of rats received escalating doses of oxytocin (0.001, 0.01, 0.1, 0.3, 1 mg/kg) administered intraperitoneally (IP) prior to daily self-administration tests, while other rats received vehicle. After these tests, lever-pressing was extinguished and the ability of methamphetamine primes (IP, 1 mg/kg) to reinstate responding was studied with and without co-administration of oxytocin (IP, 0.3 and 1 mg/kg). Results showed that oxytocin dose-dependently reduced responding for intravenous methamphetamine with an almost complete absence of responding at the highest oxytocin dose (1 mg/kg). Hyperactivity during methamphetamine self-administration was also dose-dependently reduced by oxytocin. Oxytocin (1 but not 0.3 mg/kg) also reduced the ability of methamphetamine to reinstate methamphetamine-seeking behaviour. In separate tests, oxytocin (IP, 0.3 and 1 mg/kg) robustly decreased the hyperactivity and rearing induced by methamphetamine challenge (IP, 1 mg/kg), producing activity levels similar to control animals. This study suggests that oxytocin may have a powerful inhibitory effect on the motivation to consume methamphetamine and on hyperactivity associated with acute methamphetamine intoxication. These results point to the potential utility of human trials of oxytocin as a therapeutic treatment for methamphetamine addiction.
Abstract: OBJECTIVE: The aim of this study was to provide an overview of a new 'phase of illness' model of care after relocation of Rozelle Hospital to the new purpose built Concord Centre for Mental Health and discuss its implementation and progress thus far. METHOD: One year after relocation, staff were asked to provide feedback of their views of the new model of care in order to identify implementation barriers and ways forward. RESULTS: The new model has clear benefits for the consumer, but there are a number of practical challenges and dilemmas emerging that necessitate some refinement and evaluation. Feedback from staff provided a wide range of opinions indicating that some were quite cynical of the new model while others were very supportive and thought that patient care was enhanced. CONCLUSIONS: Further development and consolidation of the model is required, including more education sessions and a clear mission statement at unit, hospital and community levels. Further research is also required to assess the impact and ability of the new model to deliver better patient outcomes, especially in regard to continuity of care.
Abstract: In this study, we surveyed clinical staff to ascertain their views regarding the delivery of difficult news (DDN), such as the need for lifelong medication with possible side effects, in inpatient mental health settings. Nearly all staff agreed patients had a right to information about their diagnosis, two thirds thought the doctor was the best person to inform patients of their diagnosis, and approximately half believed full diagnosis and treatment disclosure may have negative consequences. Providing hope when delivering difficult news was endorsed by almost all staff, and most took special precautions (e.g., greater monitoring) after DDN. Two thirds had never received specific training for DDN, yet most considered themselves competent in DDN. In DDN, staff usually or always considered patients' level of insight/awareness, likely distress, diagnosis, and whether they would understand the consequences of the diagnosis.
Abstract: Bullying activities can be overt and intimidating or comparatively invisible to others. Nurses who work in a culture of bullying may experience job dissatisfaction and physiological and psychological consequences. Failure to adhere to professional responsibilities and engage in acceptable interpersonal behaviours sets the scene for unhealthy workplaces. Bullying is also costly to organisations due to increased leave and nurse attrition and decreased nurse productivity, satisfaction, and morale. This review provides an overview of bullying, how this impacts on nursing staff, and ways to reduce bullying incidents to cultivate a more positive work environment.
Abstract: Stigmatising attitudes are not uncommon among mental health professionals who may be less than optimistic about outcomes for people with long-term mental health problems. These perceptions are probably related to the professionals' experiences, such as those working in the public sector dealing with clients in the most disturbed phases of mental illness. We provide an overview of stigma and some contemporary stigma conceptualisations and then explore some stigma-reducing strategies for mental health professionals. The way that mental health professionals work with patients can have an important effect on their recovery.
Abstract: PURPOSE.  There are numerous barriers to improving healthcare delivery. This article summarizes contemporary theories and research evidence to focus on ways to motivate change within the hospital system to provide better health care. CONCLUSIONS.  Understanding multidisciplinary team processes, recognizing hospitals as systems, and ascertaining the unit culture is a prerequisite for leaders and policy makers to improve mental health practices. PRACTICE IMPLICATIONS.  Finding ways to deliver better health care to people with a mental illness is a high priority, and nurses have a central role to play in this pursuit of excellence.
Abstract: Considerable research documents the health consequences of psychosis and co-occurring substance use disorders. Results of randomized controlled trials assessing the effectiveness of psychosocial interventions for persons with dual diagnoses are equivocal but encouraging. Many studies are hampered by small, heterogeneous samples, high attrition rates, short follow-up periods, and unclear description of treatment components. The treatments available for this group of patients (which can be tailored to individual needs) include motivational interviewing, cognitive-behavioral therapy, contingency management, relapse prevention, case management, and skills training. Regardless of whether services follow integrated or parallel models, they should be well coordinated, take a team approach, be multidisciplinary, have specialist-trained personnel (including 24-hour access), include a range of program types, and provide for long-term follow-up. Interventions for substance reduction may need to be further developed and adapted for people with serious mental illnesses. Further quality trials in this area will contribute to the growing body of data of effective interventions.
Abstract: OBJECTIVES: The objectives were, first, to determine attitudes towards psychiatry as a career among medical students currently enrolled at the University of Sydney and, second, to establish the immediate impact on those attitudes of a promotional DVD, released by the Royal Australian and New Zealand College of Psychiatrists. METHOD: Medical students enrolled in the University of Sydney in 2008 were invited to complete a voluntary online questionnaire, in which their attitudes towards psychiatry were explored, and the immediate effects of a 15-minute DVD were ascertained. RESULTS: A total of 123 students participated. Only one student identified psychiatry as their chosen career. Medical students viewed psychiatry as the least attractive specialty for the degree to which patients are helped effectively and in terms of having a reliable scientific foundation. However, it rated well in regard to being intellectually challenging, a rapidly advancing field of medicine, and providing research opportunities and a good lifestyle. Psychiatry is less respected than most other specialties by students and they perceive this discipline to be poorly respected by other medical students and current medical practitioners. After viewing the DVD, there were improved student ratings of the benefits of a career in psychiatry, especially in relation to the specialty being enjoyable, offering effective treatment and having a scientific foundation. There was also enhanced understanding of the role of a psychiatrist in just over half of the participants and increased interest in psychiatry in about 30% of participants. The DVD was most effective in increasing awareness of the diversity of subspecialties available within psychiatry, good lifestyle factors, and the training involved. CONCLUSION: Among medical students, psychiatry is perceived as unattractive and fails to command the respect afforded other specialties. The viewing of a promotional DVD by medical students was found to be effective in improving their attitudes towards psychiatry and increasing their interest in pursuing a career in the specialty. However, the long-term impact of this modest improvement is unknown and the low survey response rate limits the extent to which the results can be generalized.
Abstract: AIM: This study is a report of a systematic review to assess current evidence for the efficacy of psychosocial interventions for reducing substance use, as well as improving mental state and encouraging treatment retention, among people with dual diagnosis. BACKGROUND: Substance misuse by people with a severe mental illness is common and of concern because of its many adverse consequences and lack of evidence for effective psychosocial interventions. DATA SOURCES: Several electronic databases were searched to identify studies published between January 1990 and February 2008. Additional searches were conducted by means of reference lists and contact with authors. REVIEW METHODS: Results from studies using meta-analysis, randomized and non-randomized trials assessing any psychosocial intervention for people with a severe mental illness and substance misuse were included. RESULTS: Fifty-four studies were included: one systematic review with meta-analysis, 30 randomized controlled trials and 23 non-experimental studies. Although some inconsistencies were apparent, results showed that motivational interviewing had the most quality evidence for reducing substance use over the short term and, when combined with cognitive behavioural therapy, improvements in mental state were also apparent. Cognitive behavioural therapy alone showed little consistent support. Support was found for long-term integrated residential programmes; however, the evidence is of lesser quality. Contingency management shows promise, but there were few studies assessing this intervention. CONCLUSION: These results indicate the importance of motivational interviewing in psychiatric settings for the reduction of substance use, at least in the short term. Further quality research should target particular diagnoses and substance use, as some interventions may work better for some subgroups.
Abstract: gamma-Hydroxybutyrate (GHB) is a euphoric, prosocial and sleep inducing drug that binds with high affinity to its own GHB receptor site and also more weakly to GABA(B) receptors. GHB is efficacious in the treatment of narcolepsy and alcoholism, but heavy use can lead to dependence and withdrawal. Many effects of GHB (sedation, hypothermia, catalepsy) are mimicked by GABA(B) receptor agonists (e.g. baclofen). However other effects (euphoric and prosocial effects and a therapeutic effect in narcolepsy) are not. The present study used Fos immunohistochemistry to assess the neural activation produced in rat brain by medium to high doses of GHB (250, 500 and 1000 mg/kg) and a high dose of baclofen (10 mg/kg) that produced similar sedation to 500 mg/kg GHB. Results showed many common regions of activation with these two drugs including the supraoptic, paraventricular, median preoptic and ventral premammillary nuclei of the hypothalamus, the central nucleus of the amygdala, Edinger-Westphal nucleus, lateral parabrachial nucleus, locus coeruleus, and nucleus of the solitary tract. GHB (500 mg/kg), but not baclofen (10 mg/kg), induced significant Fos expression in the median raphe nucleus and lateral habenula, while a higher dose of GHB (1000 mg/kg) induced additional Fos expression in the islands of Calleja, dentate gyrus (polymorphic layer) and arcuate nucleus, and in various regions implicated in rapid and non-rapid eye movement sleep (laterodorsal tegmental nucleus, tuberomammillary nucleus and the ventrolateral and anterodorsal preoptic nuclei). Surprisingly, Fos immunoreactivity was not observed with either GHB or baclofen in reward-relevant regions such as the nucleus accumbens, striatum and ventral tegmental area. Overall these results indicate a distinctive signature of brain activation with GHB that may be only partly due to GABA(B) receptor effects. This confirms a unique neuropharmacological profile for GHB and indicates key neural substrates that may underlie its characteristic influence on sleep, body temperature, sociability and endocrine function.
Abstract: The popular drug 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy", "the Love Drug") produces feelings of love and closeness in humans and induces analogous prosocial and antiaggressive effects in laboratory animals. Here we examined the specific brain regions that may be involved in these prosocial effects. Male Wistar rats were pretreated with a moderate dose of MDMA (5 mg/kg) or vehicle and then either kept alone in a familiar test chamber for 60 min (groups MDMA-ALONE and VEHICLE-ALONE) or allowed to engage in social interaction in the familiar test chamber with an unfamiliar same-sex conspecific for 60 min (groups MDMA-SOCIAL and VEHICLE-SOCIAL). Rats in the MDMA-SOCIAL group showed much greater overall social interaction than rats in the VEHICLE-SOCIAL group, with microanalysis revealing increased general investigation of other rats but decreased anogenital sniffing. Analysis of neural activation across 39 brain regions using Fos immunohistochemistry showed the following results: (1) VEHICLE-SOCIAL and VEHICLE-ALONE groups did not differ in Fos expression, indicating that a social context per se did not affect Fos expression, (2) MDMA-treated groups showed significantly increased Fos expression relative to VEHICLE treated groups in 30 brain regions, (3) the MDMA-SOCIAL group showed augmented Fos expression relative to the MDMA-ALONE group in six brain regions including the caudate-putamen (medial), medial preoptic area, paraventricular thalamic nucleus, central amygdala, ventromedial hypothalamic nucleus, and the medial amygdala (posterodorsal), and (4) the MDMA-SOCIAL group (but not the MDMA-ALONE group) showed augmented Fos expression relative to the VEHICLE groups in the nucleus accumbens, ventral tegmental area and periaqueductal grey. These results indicate that a moderate dose of MDMA given in a social context causes considerably greater brain activation than the same dose given to solitary rats. This activation involves specific neural circuits that are known to regulate affiliative behavior, perhaps by modulating the incentive value of social stimuli. A possible role for the neuropeptide oxytocin in mediating the prosocial effects of MDMA is discussed.
Abstract: OBJECTIVE: This study measured patient satisfaction levels and staff views regarding their expectations and workplace and other opinions after relocation to a new purpose-built mental health facility within the grounds of a general repatriation hospital. METHOD: Patients were interviewed face-to-face using a standardized satisfaction survey at least 2 months after the move to the new facility. In addition, surveys were sent by mail to all clinical staff rostered to work the same period that the patient interviews were conducted. RESULTS: One hundred patients were interviewed and 123 staff returned the survey (56% response rate). Patients and staff rated the new ward environment and food services most highly and were least satisfied with patient information and medical services. Less satisfaction was expressed about resource issues such as information technology and dedicated staff facilities. Most staff (70-80%) rated services provided to patients to be the same or better than their original expectations. CONCLUSIONS: The results indicate that the hospital move did not have any measurable negative impact on overall service provision or patient satisfaction. In fact, expectations were met or improved for several clinically relevant areas after relocating the mental health facility. Another survey is planned in 12 months to assess if patient and staff ratings change.
Abstract: With the development of peer support networks in the mental health system, formal training should be provided regarding the adverse effects of substance use. Four educational workshops were conducted with caregivers and consumer workers to increase their knowledge and confidence to support people with a dual diagnosis. Workshops were evaluated through presurvey and postsurvey. The workshops were well received, and postworkshop, participants reported fewer negative attitudes toward people with a dual diagnosis and increased understanding and knowledge regarding substance misuse. This study highlights the effectiveness of targeted workshops for caregivers and consumer workers and advocates that nurses take a more active role in educational projects involving stakeholders.
Abstract: INTRODUCTION AND AIMS: Substance misuse by people with a serious mental illness may exacerbate psychiatric symptoms and contribute to relapse. The aim of the study was to ascertain the views of a wide range of Australian mental health service providers on staff education and training, client contact and management, assessment, and treatment effectiveness and service delivery. DESIGN AND METHODS: A survey was sent to a sample of 171 mental health stakeholders in Australia identified through internet searches, state and territory mental health departments and professional organisations. RESULTS: Of the 66 respondents (39% response rate), the substances identified to be most problematic were alcohol and cannabis. Integrated service models of treatment were identified as the most preferable and effective. Barriers to treatment included client motivation to reduce substance use, poor communication and coordination between treatment services, and lack of specific services for dual diagnosis clients. Almost all indicated a need for further training in the area of dual diagnosis. DISCUSSION AND CONCLUSIONS: Dual diagnosis is common and the reality is that this vulnerable clientele will continue to challenge service providers and treatment approaches into the foreseeable future. Issues include the organization and delivery of treatment services, education and training, resource allocation, collaboration between treatment agencies and clinically relevant research evaluating the effectiveness of practice. It is thus surprising that with so much investment in this area the majority of stakeholders are still dissatisfied with access to and the level of care for dual diagnosis clients.
Abstract: Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with gamma-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 degrees C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA.
Abstract: Access to the most relevant articles with recent evidence is essential for writing peer-reviewed articles and informing clinical decision making. A clear method is needed to undertake a mental health literature review to ensure the topic is covered adequately. Choosing the right key words and search strategies and using appropriate databases are essential starting points. Drawing on different search methods to access a variety of sources ensures the most relevant articles are retrieved for a high-quality clinical literature review. Advanced searching includes the use of the medical subject headings thesaurus and other strategies to refine and focus the search for optimum sensitivity and specificity. Regardless of whether a search is basic or advanced, stages of the search procedures, such as determining key terms, databases used and the date range used within each, fields selected, dates of access, a history of search sets, and the justification for excluding data, should be documented to provide an audit trail. This article provides an overview of these search steps.
Abstract: Recent reports indicate an absence of respect in workplace culture. Every person has the right to a workplace that is fair and equitable and in which he or she is treated with respect and dignity. Working in a collegial manner is challenging when environments have staff who engage in unprofessional or disruptive behaviors. A number of steps can be taken to support a healthy workplace and prevent bullying. Healthy workplaces are ones in which leaders and managers lead by example, champion respect, and set the tone and expectation for behaviors essential for fostering a harmonious and collaborative environment. The role of the leader/manager is crucial in developing a positive workplace culture that supports a high level of professionalism and a culture of zero tolerance toward bullying.
Abstract: Cat odor elicits defensive responses in rats that are modified by repeated exposure to the odor. We explored the neural correlates of this adaptation using FosB/DeltaFosB immunohistochemistry. Rats were given 3 x60 min exposures to either a worn cat collar (repeated cat odor group) or unworn cat collar (control group). Each exposure was separated by 48h. Rats exposed to cat odor initially showed strong defensive responses (decreased contact, increased retreat, and increased fecal pellets), however these responses had habituated by the final exposure. Rats were perfused 24h or 7 days after the final exposure and the brains were processed for FosB/DeltaFosB protein expression. Up-regulation of FosB/DeltaFosB was observed 24h after repeated cat odor exposure in the nucleus accumbens core, caudate putamen, ventrolateral periaqueductal gray, and four hypothalamic regions: lateral hypothalamus, ventromedial hypothalamus, anterior hypothalamic nucleus, and dorsal premammillary nucleus. FosB/DeltaFosB expression remained elevated 7 days after repeated cat odor exposure in the nucleus accumbens core, caudate putamen and anterior hypothalamic nucleus. These findings provide initial evidence that behavioral changes occurring as a result of repeated predatory stress are associated with long-lasting regionally specific neuroadaptations in the brain.
Abstract: Communication research and investigations into the delivery of bad news are uncommon in psychiatry versus other medical specialties. The question of delivering "bad" diagnostic news in psychiatry has been focused on dementia rather than actual psychiatric disorders and their sequelae. Common problems are that psychiatrists avoid dealing with patients' emotional reactions to bad news and that they avoid providing a clear diagnosis for fear that patients or carers will be distressed. This article aims to provide an overview of key elements of the "breaking bad news" literature, teasing out factors that are relevant to psychiatric practice. Topics explored include: definitions; clinical considerations for delivering difficult news within medical and psychiatric settings; protocols and guidelines; evidence about patient information needs and communication preferences; research into actual delivery of such news; and areas for future education and research.
Abstract: Locked inpatient units are an increasing phenomenon, introduced in response to unforseen abscondences and suicides of patients. This paper identifies some value issues concerning the practice of locked psychiatric inpatient units. Broad strategies, practicalities and ethical matters that must be considered in inpatient mental health services are also explored. The authors draw on the published research and commentary to derive relevant information to provide to patients and staff regarding the aims and rationales of locked units. Further debate is warranted in relation to best practice. Inpatient staff need to be aware of their practice values, be able to access education and supervision and negotiate apparent contradictions. Further patient/clinician focused enquiry is necessary to mitigate the negative and stigmatising effects of locked mental health units.
Abstract: Cat odor and trimethylthiazoline (TMT, a component of fox feces) are two stimuli widely used in rodent models of fear and anxiety. Recent studies suggest that these odorants have distinct behavioral effects, raising questions as to whether TMT is a true "predator odor." Here we used c-Fos immunohistochemistry to compare patterns of neural activation produced by cat odor and TMT. Rats were exposed to either (1) three pieces of a collar that had been worn by a domestic cat, (2) three collar pieces impregnated with TMT (30 microl/piece), (3) three collar pieces impregnated with 4% formaldehyde (200 microl/piece, an acrid but non-predatory odor), or (4) three control (no odor) collar pieces. Odors were presented in a small well-ventilated plastic box. All odorants (cat odor, TMT and formaldehyde) produced increased defecation in rats compared with the control group, and formaldehyde exposure also decreased rearing. Cat odor increased contact with the stimulus relative to all other groups, while TMT increased contact compared with the formaldehyde and clean air groups. Only cat odor decreased grooming and elicited escape attempts. In addition, only cat odor caused pronounced activation of Fos in the accessory olfactory bulb and its projection areas, anterior olfactory nucleus, medial prefrontal cortex, striatum, and a medial hypothalamic circuit associated with defensive behavior. In contrast, the only areas activated by TMT were the internal granular layer of the main olfactory bulb and central amygdala, while both cat odor and TMT activated the glomeruli of the main olfactory bulb, piriform cortex, ventral orbital cortex and anterior cortical amygdala. Results indicate that the effects of cat odor and TMT are easily distinguished both behaviorally and at a neural level, and suggest that TMT lacks the "pheromone-like" quality of cat odor that engages key hypothalamic sites involved in defensive behavior.
Abstract: OBJECTIVE: The aim of this study was to ascertain the experiences, views and monitoring practices of Australian child psychiatrists regarding the metabolic and other side effects of second-generation antipsychotics (SGAs). METHOD: A 19-item questionnaire was posted to all members of the RANZCP Faculty of Child and Adolescent Psychiatry living in Australia. RESULTS: Of the 290 eligible members of the Faculty of Child and Adolescent Psychiatry, 126 (43%) returned a useable survey. SGAs are commonly prescribed for a range of disorders. The majority of respondents expressed a high level of concern regarding weight gain and other metabolic side effects. Weight gain was the most frequently observed and monitored side effect in clinical practice. Other side effects were observed and monitored to a variable extent. Notably, monitoring practices did not parallel psychiatrists' reported level of concern or knowledge regarding weight gain and metabolic side effects,nor coincide with published recommendations. CONCLUSIONS: Further research is required into the use, efficacy, side effects and monitoring of SGAs in children and adolescents, and there is a need to ensure that monitoring guidelines are implemented in clinical practice. This need is heightened by the likelihood that our data on clinicians' practice, which is based on their perceptions, may overestimate what actually occurs.
Abstract: Working with and treating individuals with co-occurring substance misuse presents unique challenges for mental health nurses. Substance misuse is common in mental health settings, and its clinical challenges with system barriers impede positive treatment outcomes. To work effectively in everyday clinical practice with dual diagnosis clients, nurses need to consider potential guiding principles. These principles pertain to treatment aims, engagement, assessment, symptoms, care plans, cycle of change, motivational interviewing, traps to avoid, active treatment, relapse prevention, agency collaboration, and treatment diversity. Clinical tools are easily accessible resources that can provide a framework for contemporary practice in a range of settings. Such resources are helpful in practice and as a foundation for orientation, education, self-reflection, and peer review. Setting expectations for everyday practice and ensuring that clients with a dual diagnosis receive the best care possible are important goals for the nursing profession.
Abstract: The influence of substance use on patient's needs and caregiving consequences has received insufficient research attention. We sought to determine whether patients with comorbid substance use have higher levels of need, anxiety, depression, and caregiving consequences than those of patients who do not use substances. A total of 520 patients participated, and those who used substances (n = 216) reported higher levels of unmet needs, anxiety, and caregiving consequences than did patients who did not use substances. Carers of patients who used substances also reported higher anxiety and more caregiving consequences. Very few patients were actively involved in treatment programs to reduce their substance use.
Abstract: BACKGROUND: Even low levels of substance misuse by people with a severe mental illness can have detrimental effects. OBJECTIVES: To assess the effects of psychosocial interventions for substance reduction in people with a serious mental illness. SEARCH STRATEGY: For this update (2007) we searched the Cochrane Schizophrenia Group Trials Register (May 2006) which is based on regular searches of major databases. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where data were homogeneous. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. MAIN RESULTS: Evaluation of long-term integrated care included 4 RCTs (total n=735). We found no significant difference on measures of substance use (n=85, 1 RCT, RR 0.89 CI 0.6 to 1.3) or loss to treatment (n=603, 3 RCTs, RR 1.09 CI 0.8 to 1.5). For the non-integrated intensive case management trials (4 RCTs, total n=151) we also found no significant difference for loss (n=134, 3 RCTs, RR 1.35 CI 0.8 to 2.2). Motivational interviewing plus cognitive behavioural therapy (3 RCTs, total n=276) did not reveal any advantage for retaining participants (n=36, 1 RCT, RR lost to treatment 0.50 CI 0.1 to 5.0) or for relapse (n=36, 1 RCT, RR 0.58 CI 0.3 to 1.1), and no benefit for reducing substance use (n=119, 1 RCT, RR 0.19 CI -0.2 to 0.6). Cognitive behavioural therapy alone (4 trials, total n=260) showed fewer participants lost from treatment (n=260, 4 RCTs, p=0.02, RR 0.61 CI 0.4 to 0.9). No benefits were observed on measures of lessening cannabis use (n=47, 1 RCT, RR 1.30 CI 0.8 to 2.2) or on the number of participants using substances (alcohol; n=46, 1 RCT, RR 5.88 CI 0.8 to 44.0, drugs; n=46, 1 RCT, RR 2.02 CI 0.9 to 4.8) and no differences were observed on measures of mental state (n=105, 1 RCT, RR 0.52 CI -0.8 to 1.8). We found no advantage for motivational interviewing alone (5 trials, total n=338) in reducing 'lost to evaluation' (n=338, 5 RCTs, RR 0.96 CI 0.6 to 1.5) compared with treatment as usual, although significantly more participants in the motivational interviewing group reported for their first aftercare appointment (n=93, 1 RCT, RR 0.69 CI 0.5 to 0.9, NNT 4 CI 3 to 12). Some differences were observed in abstaining from alcohol favouring treatment (n=28, 1 RCT, RR 0.36 CI 0.2 to 0.8, NNT 2 CI 2 to 5), but not other substances (n=89, 1 RCT, RR -0.07 CI -0.6 to 0.4) and no differences were observed in mental state (n=30, 1 RCT, WMD -4.20 CI -18.7 to 10.3). Finally, we found no significant differences for skills training in the numbers lost to treatment by 12 months (n=94, 2 RCTs, RR 0.70 CI 0.4 to 1.1). AUTHORS' CONCLUSIONS: We included 25 RCTs and found no compelling evidence to support any one psychosocial treatment over another to reduce substance use (or improve mental state) by people with serious mental illnesses. Furthermore, methodological difficulties exist which hinder pooling and interpreting results; high drop out rates, varying fidelity of interventions, varying outcome measures, settings and samples and comparison groups may have received higher levels of treatment than standard care. Further studies are required which address these concerns and improve the evidence in this important area.
Abstract: The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.
Abstract: Increasingly, consumers and carers are involving themselves in many aspects and levels of mental health services. However, one area in which active involvement has been less prominent is research. This paper describes an educational initiative that sought to increase consumers' and carers' understanding of the way research is conducted and its role in evidence-based practice. Information regarding participants' attitudes towards research, knowledge about research practice and participation was also examined. The findings provide evidence that workshop attendance increases knowledge and encourages participation in future research projects, particularly when participants have confidence in the researcher.
Abstract: Over 50% of people with a severe mental illness also use illicit drugs and/or alcohol at hazardous levels. This review is based on the findings of 25 randomized controlled trials which assessed the effectiveness of psychosocial interventions, offered either as one-off treatments or as an integrated or nonintegrated program, to reduce substance use by people with a severe mental illness. The findings showed that there was no consistent evidence to support any one psychosocial treatment over another. Differences across trials with regard to outcome measures, sample characteristics, type of mental illness and substance used, settings, levels of adherence to treatment guidelines, and standard care all made pooling results difficult. More quality trials are required that adhere to proper randomization methods; use clinically valuable, reliable, and validated measurement scales; and clearly report data, including retention in treatment, relapse, and abstinence rates. Future trials of this quality will allow a more thorough assessment of the efficacy of psychosocial interventions for reducing substance use in this challenging population.
Abstract: Social behavior in mammals often relies upon the discrimination of same-species individuals via olfactory processing of unique chemosensory signatures. The ability to identify individuals from a different species by their odor (heterospecific discrimination) is less well documented. Here we used a habituation-dishabituation paradigm to demonstrate that rats can discriminate individual cats by their odor. Rats were repeatedly exposed to a collar previously worn by a domestic cat. Strong initial defensive responses (hiding in a small box and vigilant "head out" behavior from the box entrance) habituated with repeated exposure to the same collar. Brain activation following repeated presentation of the same odor - as indexed by c-Fos expression - also habituated in accessory olfactory regions (mitral and granular layers of the posterior accessory olfactory bulb and posteroventral medial amygdala), as well as regions involved in defensive behavior, including the ventromedial and dorsal premammillary hypothalamic nuclei, basolateral amygdala and periaqueductal grey. When a collar taken from a different cat was presented to habituated rats, defensive responses (hiding, vigilance, suppression of grooming) were dishabituated, and c-Fos expression was reinstated in the accessory olfactory system and in defense-related hypothalamic, amygdaloid and brainstem nuclei. Results indicate that rats may process and store details of the chemosensory signatures of individual predators using the accessory olfactory system.
Abstract: Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.
Abstract: The purpose of this research was to survey staff and patients about their experience, knowledge, and attitudes regarding research. One hundred and sixty patients were interviewed using a questionnaire. In addition, a modified version of the same questionnaire was sent to multidisciplinary staff (n = 476), and about two-fifths (n = 181, 38%) were returned. Participants were interested in research and keen to know more about methods and processes. There were significant differences between staff and patients in terms of attitudes towards evidence-based practice and knowledge about research. The findings support the notion that staff and patients hold similar views about research methods and influences.
Abstract: The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT(1A) antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 microg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.
Abstract: OBJECTIVES: To assess the long-term psychosocial outcomes and supportive care needs of gynecologic cancer survivors. METHODS: Women who had received care in a tertiary-based gynecologic cancer center 1-8 years earlier and who were disease-free were invited to complete a mailed self-report questionnaire to assess psychosocial outcomes and supportive care needs. RESULTS: In total, 199 survivors participated in the study. Survivors reported normal quality of life and relationship adjustment although functioning was at the lower end of the range; over two-thirds (68%) reported positive outcomes. However, nearly one-third (29%) reported clinical levels of anxiety and the most frequently endorsed need concerned fear of disease recurrence (24%). About one-fifth (19%) reported symptoms that indicated posttraumatic stress disorder (PTSD) and this rose to close to one-third (29%) for survivors of advanced stage disease. Nearly 90% of survivors reported supportive care needs and the diagnosis of anxiety or PTSD resulted in a four-fold increase in unmet needs. Needs most frequently concerned "existential survivorship" (e.g., spiritual beliefs, decision making, the meaning of life) and "comprehensive cancer care" (e.g., team care, communication, local health care services). Years since diagnosis was not related to distress or need levels. CONCLUSIONS: All members of the care team need to be aware that significant psychosocial morbidity may occur many years after the successful treatment of a gynecologic malignancy and may be associated with elevated supportive care needs. Comprehensive and extended supportive care services are required to address anxiety and trauma responses and investigate strategies to meet ongoing needs in order to improve long-term psychosocial outcomes.
Abstract: Cannabis use may increase the risk of developing schizophrenia by precipitating the disorder in genetically vulnerable individuals. Neuregulin 1 (NRG1) is a schizophrenia susceptibility gene and mutant mice heterozygous for the transmembrane domain of this gene (Nrg1 HET mice) exhibit a schizophrenia-related phenotype. We have recently shown that Nrg1 HET mice are more sensitive to the behavioral effects of the main psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC). In the present study, we examined the effects of THC (10 mg/kg i.p.) on neuronal activity in Nrg1 HET mice and wild type-like (WT) mice using c-Fos immunohistochemistry. In the lateral septum, THC selectively increased c-Fos expression in Nrg1 HET mice with no corresponding effect being observed in WT mice. In addition, THC promoted a greater increase in c-Fos expression in Nrg1 HET mice than WT mice in the central nucleus of the amygdala, the bed nucleus of the stria terminalis and the paraventricular nucleus of the hypothalamus. Consistent with Nrg1 HET mice exhibiting a schizophrenia-related phenotype, these mice expressed greater drug-free levels of c-Fos in two regions thought to be involved in schizophrenia, the shell of the nucleus accumbens and the lateral septum. Interestingly, the effects of genotype on c-Fos expression, drug-free or following THC exposure, were only observed when animals experienced behavioral testing prior to perfusion. This suggests an interaction with stress was necessary for the promotion of these effects. These data provide neurobiological correlates for the enhanced behavioral sensitivity of Nrg1 HET mice to THC and reinforce the existence of cannabinoid-neuregulin 1 interactions in the CNS. This research may enhance our understanding of how genetic factors increase individual vulnerability to schizophrenia and cannabis-induced psychosis.
Abstract: BACKGROUND: Partners of cancer patients typically provide the majority of patients' emotional and physical care. Partners may be profoundly affected by the cancer and may experience ongoing supportive care needs across the survivorship continuum. Research has been restricted by a lack of psychometrically evaluated measures and in this study, a self-report measure of partners' needs was developed and empirically evaluated. METHODS: Questionnaire items generated from a qualitative study were constructed into a 47- item unmet need measure (Cancer Survivors' Partners Unmet Needs measure, CaSPUN). The psychometric properties of the CaSPUN were evaluated in 212 partners of patients who had been diagnosed with cancer 1-11 years earlier and were currently disease-free. RESULTS: The CaSPUN was modified to include 35 unmet need items, 6 positive change items and an open ended item. The CaSPUN demonstrates a high level of acceptability, internal consistency and construct validity, although test-retest reliability was moderate. Factor analysis identified five discrete factors: (1) Relationships, (2) Information, (3) Partner Issues, (4) Comprehensive Care and (5) Emotional Support. CONCLUSIONS: The CaSPUN permits the identification of long-term supportive care needs in generic populations of cancer survivors' partners and will assist with the formulation of recommendations regarding required supportive care services.
Abstract: 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug that is often taken under hot conditions at dance clubs. High ambient temperature increases MDMA-induced hyperthermia and recent studies suggest that high temperatures may also enhance the rewarding and prosocial effects of MDMA in rats. The present study investigated whether ambient temperature influences MDMA-induced expression of Fos, a marker of neural activation. Male Wistar rats received either MDMA (10 mg/kg i.p.) or saline, and were placed in test chambers for 2 h at either 19 or 30 degrees C. MDMA caused significant hyperthermia at 30 degrees C and a modest hypothermia at 19 degrees C. The 30 degrees C ambient temperature had little effect on Fos expression in vehicle-treated rats. However MDMA-induced Fos expression was augmented in 15 of 30 brain regions at the high temperature. These regions included (1) sites associated with thermoregulation such as the median preoptic nucleus, dorsomedial hypothalamus and raphe pallidus, (2) the supraoptic nucleus, a region important for osmoregulation and a key mediator of oxytocin and vasopressin release, (3) the medial and central nuclei of the amygdala, important in the regulation of social and emotional behaviors, and (4) the shell of the nucleus accumbens and (anterior) ventral tegmental area, regions associated with the reinforcing effects of MDMA. MDMA-induced Fos expression was unaffected by ambient temperature at many other sites, and was diminished at high temperature at one site (the islands of Calleja), suggesting that the effect of temperature on MDMA-induced Fos expression was not a general pharmacokinetic effect. Overall, these results indicate that high temperatures accentuate key neural effects of MDMA and this may help explain the widespread use of the drug under hot conditions at dance parties as well as the more hazardous nature of MDMA taken under such conditions.
Abstract: BACKGROUND: Many cancer survivors experience ongoing morbidity over the survivorship continuum and their supportive care needs have yet to be comprehensively assessed. METHODS: This study aimed to develop and empirically evaluate a self-report measure of cancer survivors' supportive care needs. In Phase I, questionnaire items were generated based upon previous qualitative research that identified both unique and shared needs in survivors and their partners; items were constructed into the Cancer Survivors' Unmet Needs measure (CaSUN). In Phase 2, the CaSUN was completed by 353 cancer survivors who had been diagnosed with cancer between 1 and 15 years earlier and were currently disease-free. RESULTS: After modification, the CaSUN included 35 unmet need items, 6 positive change items and an open-ended question. Good acceptability, internal consistency and validity were demonstrated, although test-retest reliability was low. Maximum likelihood factor analysis identified five discrete factors: Existential Survivorship, Comprehensive Care, Information, Quality of Life and Relationships. CONCLUSIONS: Preliminary data indicates that the CaSUN meets the majority of psychometric criteria for assessment measures, although its low test-retest reliability awaits further investigation. The CaSUN will facilitate the evaluation of supportive care services and generation of service delivery recommendations for cancer survivors.
Abstract: In recent work we have documented lasting adverse neurochemical and behavioural effects in rats given short-term 'binge' dosing with methylenedioxymethamphetamine (MDMA, Ecstasy), methamphetamine (METH) or their combination. Here we investigated whether similar effects persist in rats given 16 weekly injections followed by a 10 week period of abstinence. Female rats received MDMA (8 mg/kg, i.p.), METH (8 mg/kg), or a MDMA/METH combination (4 mg/kg MDMA + 4 mg/kg METH), once a week for 16 weeks, with locomotor activity and body temperature measured on weeks 1, 8 and 16. The MDMA and MDMA/METH groups showed acute drug-induced hyperthermia on week 1 only. MDMA-treated rats demonstrated an acute hyperactivity while METH and MDMA/METH treated rats showed pronounced stereotypy. Seven weeks after drug-treatment concluded, a decrease in social interaction was observed in all chronically drug-treated rats. No group differences were evident on the emergence, object recognition or forced swim tests. Neurochemical analysis revealed modest noradrenaline and serotonin depletion in chronically treated rats that was not evident following a single equivalent administration. These results indicate that although chronic, intermittent exposure to MDMA, METH or their combination, may not lead to significant long-term monoamine depletion, lasting adverse behavioural effects may persist, especially those related to social behaviour.
Abstract: GOALS OF THE WORK: A significant proportion of breast cancer patients experience psychosocial morbidity after treatment, although their longer-term outcomes and supportive care service needs have not been comprehensively documented. The aim of this study was to identify longer-term outcomes and supportive care needs in disease-free breast cancer survivors. MATERIALS AND METHODS: One hundred seventeen patients who had been diagnosed with breast cancer 2-10 years earlier completed questionnaires to assess psychosocial outcomes including supportive care needs, psychological distress, and quality of life (QoL). MAIN RESULTS: QoL and depression scores were consistent with community rates although anxiety scores were higher. Approximately two thirds of survivors reported at least one unmet need, most frequently concerning existential survivorship issues, thereby highlighting the unique needs of survivors. Years since diagnosis was not correlated with need levels. Survivors classified as clinically anxious reported over three times as many unmet needs and survivors classified as depressed reported over two and a half times as many unmet needs. Positive outcomes were frequently reported. CONCLUSIONS: The findings have direct clinical relevance: irrespective of years since diagnosis, comprehensive and extended supportive care services are required to identify breast cancer survivors in need of supportive care interventions and remediate high levels of anxiety.
Abstract: GOALS OF WORK: Partners of cancer patients may experience significant distress at the time of treatment and many may experience persistent difficulties, although little research has examined their longer term psychosocial outcomes or supportive care needs. MATERIALS AND METHODS: One hundred and fifty-four cancer survivors who were 1-11 years post diagnosis and disease-free and their partners completed mailed questionnaires. MAIN RESULTS: A positive relationship was found between psychological distress and supportive care needs both within and between partner and survivor samples. Partners reported high levels of anxiety and supportive care needs, most frequently concerning relationships and the impact of the cancer illness. Partners within couples reported both shared and unique needs, although agreement on ratings of shared needs was low. Needs did not diminish over time although partners demonstrated psychological resilience and reported positive outcomes. Predictors of distress and unmet needs were explored: physical QOL, relationship satisfaction, and total needs contributed to variability in partners' distress; relationship satisfaction and total needs were associated with survivors' distress. Distress and relationship satisfaction were associated with partners' unmet needs; only distress was associated with survivors' unmet needs. CONCLUSIONS: Partners are not merely providers of support, but need support themselves many years after a cancer diagnosis and in the context of apparently cured disease. The quality of the dyadic relationship may be critical in determining both partner and survivor distress and needs, and may prove a useful target for psychosocial interventions.
Abstract: The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and methamphetamine (METH, 'ice', 'speed') are increasingly popular drugs amongst party-drug users. Studies with humans have investigated the acute and possible long-term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long-term effects of MDMA and METH on brain and behaviour. Self-administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long-term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a 'neurotoxic' effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long-term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs.
Abstract: The combined use of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') with methamphetamine (METH) by recreational drug users is of particular concern due to their similar pharmacological and toxic profiles. In the current study we sought to elucidate why combining these particular drugs is such a popular choice among party-drug users. This was investigated through characterisation of the possible interactive effects of MDMA on METH intravenous self-administration. The first experiment involved characterisation of the METH dose-response curve for intravenous self-administration. Male Hooded-Wistar rats were trained to self-administer intravenous METH (0.01-0.3 mg/kg/infusion) and an inverted-U dose-response curve was obtained. In Experiment 2, a second squad of rats self-administered 0.01, 0.03 or 0.1 mg/kg/infusion METH and had small amounts of MDMA (0.001-0.03 mg/kg) then introduced into the infusion solution. Addition of MDMA to the METH infusion solution resulted in a dose independent reduction in responding. In Experiment 3, a third squad of rats was treated 20 min pre-session with an intraperitoneal injection of saline, 1.25 or 2.5 mg/kg of MDMA or METH to evaluate whether the reduction in responding evident in Experiment 2 was due to an MDMA-induced decrease in locomotor activity. Pre-treatment with intraperitoneal MDMA or METH had no effect on METH self-administration nor activity. We hypothesise that the reduction in METH self-administration caused by MDMA may reflect inhibitory effects of MDMA-induced 5-HT release on dopaminergic mechanisms.
Abstract: OBJECTIVE: To identify patients' and carers' perceptions of need in inpatient and community settings and investigate the relationship between need and caregiver burden. METHOD: The study was conducted across a metropolitan mental health service in Sydney, Australia. Patients (n = 407) and carers (n = 50) completed the Camberwell Assessment of Need Short Appraisal Schedule. Carers also completed a shortened version of the Involvement Evaluation Questionnaire to assess caregiver burden. RESULTS: When completing the assessment tools, patients and carers in hospital settings were asked to consider the 4 weeks preceding hospitalisation; in the community, patients and carers were asked to consider the previous 4 weeks. These data show a high percentage of patients in hospital and community settings have unmet needs for company, daytime activities and intimate relationships. Inpatients had more unmet needs than community based patients. Agreement between patients' and carers ratings' of need ranged from 'poor' to 'moderate'. There was a strong relationship between unmet need and burden from the carer's perspective. Patients with and without carers had similar numbers of needs. Carers of patients recently admitted to hospital reported a significantly higher burden. CONCLUSIONS: Carers of inpatients experienced significantly more burden than carers of outpatients. Opportunities to access support, information and education should be readily available and not contingent upon demonstrating a close familial relationship to the patient. We found that unmet need was significantly related to burden, suggesting that meeting patient needs could reduce carer burden.
Abstract: This cross-sectional study was conducted across inpatient facilities of a metropolitan mental health service in Sydney, Australia. Given shorter lengths of stay in acute inpatient facilities, it is important to ascertain differences between patients' and carers' perceptions of need and support in order to guide delivery of care in the community. The objectives were to: (1) assess the needs of patients recently admitted to hospital and ascertain the level of carer involvement while in hospital; (2) compare the degree of agreement between patients' and carers' perceptions of need and caregiver burden; and (3) determine the relationship between levels of need and carer burden prior to hospitalization. Over a 2-month period, consecutive patients (n = 200) were interviewed using the Camberwell Assessment of Need Short Appraisal Schedule and a modified version of the Involvement Evaluation Questionnaire to assess basic needs and patient perceptions of caregiver burden, respectively. Of the 200 patients interviewed, 68% (n = 135) identified a carer. Patients with schizophrenia had most met needs, those with affective disorders had most unmet needs and patients with other diagnoses recorded the lowest number of needs overall. The level of agreement between patient and carer perceptions of need was low, possibly because of confusion about the definition of need or different views about the support required to fulfil a need. Patients underestimated the consequences of caregiving, especially the impact of strained atmosphere, global burden, worrying about their future and encouragement to undertake an activity, indicating that carers were more burdened than patients perceived them to be.
Abstract: The acute and long-term dangers of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and methamphetamine (METH) are well described individually, but their effect in combination is largely unknown. Here groups of female rats were given four MDMA or METH injections within a single session with each injection separated by 2h. Treatments included MDMA only, METH only, MDMA and METH in a cocktail (MDMA/METH), MDMA (two injections) followed by METH (two injections) (MDMA-->METH), or METH followed by MDMA (METH-->MDMA). Each injection involved 4mg/kg of total drug. Drug administration occurred at a high ambient temperature of 28 degrees C. All treatments produced hyperactivity while the treatments where MDMA was administered first (MDMA, MDMA-->METH and MDMA/METH) produced hyperthermia. All treatments involving METH caused significant head weaving. Six weeks after drug treatment all groups showed reduced social interaction relative to controls. MDMA/METH treatment was associated with reduced swimming in the forced swim test. MDMA given alone caused 5-HT depletion in several brain regions while METH given alone caused dopamine depletion in the striatum. The three treatments involving MDMA and METH combinations caused significant depletion of serotonin, dopamine and noradrenaline in several brain regions. Interestingly, the MDMA-->METH treatment produced greater hippocampal and cortical 5-HT depletion than the METH-->MDMA treatment suggesting an effect of order. These results extend our recent findings of additive toxic effects when METH is combined with MDMA. This has potentially important implications for party drug users who appear to frequently use this combination.
Abstract: In recent years, efforts have been directed towards making mental health nursing more evidence-based. Making evidence based practice (EBP) a reality in modern health services requires due attention to service planning and management. It is acknowledged that there are many challenges and barriers to implementing EBP as outlined in this article. However, by using an example from our mental health service and drawing upon the literature, we show that a variety of techniques can be used to incorporate EBP into everyday practice. A combination of approaches is recommended, including education and training, leadership programs, research units, dissemination of research findings and structural changes to draw upon the expertise of key clinical, education, management and research staff.
Abstract: Positive and effective consumer outcomes hinge on having in place optimal models of nursing care delivery. The aim of this study was to ascertain the experience and views of mental health nurses, working in hospitals in an area mental health service, regarding nursing care delivery in those settings. Surveys (n = 250) were sent to all mental health nurses working in inpatient settings and 118 (47%) were returned. Results showed that the quality of nursing care achieved high ratings (by 87%), and that two-thirds of respondents were proud to be a mental health nurse and would choose to be a mental health nurse again. Similarly, the majority (71%) would recommend mental health nursing to others. Concern was, however, expressed about the continuity and consistency of nursing work and information technology resources. Nurses with community experiences rated the importance of the following items, or their confidence, higher than those without previous community placements: the importance of interdisciplinary teamwork; the importance of participating in case review; the importance of collaborating with community staff; confidence in performing mental state examinations; and confidence in collaborating with community staff, suggesting that this placement had positive effects on acute care nursing.
Abstract: Exposure to cat odor, an innate threat stimulus for rats, engages a conditioning process whereby the environment in which the odor was experienced comes to elicit fear. Additionally, response to cat odor appears to change with repeated exposure, with benzodiazepines having an anxiolytic effect upon first, but not second, cat odor exposure. We explored the neural correlates of these two phenomena using Fos immunohistochemistry. Rats were exposed to cat odor (a worn cat collar) and were allowed to hide from this stimulus. A 'trial 1' group was perfused after a single exposure, and a 'trial 2' group after two exposures. A 'context' group was exposed to cat odor once, then perfused after re-exposure to the odor-paired context. Trial 1, trial 2 and context groups showed similar defensive responses including avoidance and hiding. The trial 1 group showed Fos expression in limbic, hypothalamic and brainstem regions associated with defensive behavior. The trial 2 group showed a similar pattern although with less activation in the lateral septum, anterior and ventromedial hypothalamus, and dorsolateral periaqueductal gray. The context-exposed group showed Fos expression in a subset of the regions activated by cat odor itself: the dorsal premammillary nucleus, ventrolateral periaqueductal grey, cuneiform nucleus and locus ceruleus. Little activation was seen in the amygdala or hippocampus. These results show that stimuli associated with predatory threat come to activate similar brain regions to the threat stimulus itself.
Abstract: OBJECTIVE: The objectives of this study were to: (i) obtain baseline data on the extent of carer involvement across a representative sample of hospital and community patients within an integrated area health service; and (ii) examine perspectives on discharge planning and community care among patients and their carers to identify information and resources they consider important. METHOD: Over a 4-month period, inpatients before discharge and patients accessing community mental health services participated in face-to-face interviews. Information was collected about carer involvement and, with the patient's consent, the identified carer was sent a similar survey to determine demographics and information needs. This resulted in a representative sample of patients and carers accessing inpatient and community settings across a metropolitan mental health service. Support needs and carer burden were also assessed but are not reported here. RESULTS: A total of 407 interviews were completed, 207 in inpatient settings and 200 in the community. An inpatient response rate of 70% and a community response rate of 75% was achieved. Across both settings, 67% of patients identified a carer and a carer response rate of 28% was then obtained. We found carers and patients have different priorities regarding the information they want and information is often not provided to carers. Furthermore, patients were more confident in their ability to manage their mental health in the community than carers. CONCLUSIONS: This study yielded important baseline data about the number of patients who have a carer. We were also able to determine that routine clinical information provided to patients and carers is inadequate from their perspective. It is anticipated that this initiative will assist ongoing service planning and improve partnerships with patients and their carers.
Abstract: RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are illicit drugs that are increasingly used in combination. The acute and long-term effects of MDMA/METH combinations are largely uncharacterised. OBJECTIVES: The current study investigated the behavioural, thermal and neurotoxic effects of MDMA and METH when given alone or in combined low doses. METHODS: Male rats received four injections, one every 2 h, of vehicle, MDMA (2.5 or 5 mg/kg per injection), METH (2.5 or 5 mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per injection or 2+2 mg/kg per injection). Drugs were given at an ambient temperature of 28 degrees C to simulate hot nightclub conditions. Body temperature, locomotor activity and head-weaving were assessed during acute drug administration while social interaction, anxiety-related behavior on the emergence test and neurochemical parameters were assessed 4-7 weeks later. RESULTS: All treatments acutely increased locomotor activity, while pronounced head-weaving was seen with both MDMA/METH treatments and the higher dose METH treatment. Acute hyperthermia was greatest with the higher dose MDMA/METH treatment and was also seen with MDMA but not METH treatment. Several weeks after drug administration, both MDMA/METH groups, both METH groups and the higher dose MDMA group showed decreased social interaction relative to controls, while both MDMA/METH groups and the lower dose MDMA group showed increased anxiety-like behaviour on the emergence test. MDMA treatment caused 5-HT and 5-HIAA depletion in several brain regions, while METH treatment reduced dopamine in the prefrontal cortex. Combined MDMA/METH treatment caused 5-HT and 5-HIAA depletion in several brain regions and a unique depletion of dopamine and DOPAC in the striatum. CONCLUSIONS: These results suggest that MDMA and METH in combination may have greater adverse acute effects (head-weaving, body temperature) and long-term effects (decreased social interaction, increased emergence anxiety, dopamine depletion) than equivalent doses of either drug alone.
Abstract: OBJECTIVE: The primary aim of this study was to describe high support accommodation services available for patients with chronic mental illness living in New South Wales (NSW). The second aim was to ask patients in these facilities about their needs and satisfaction with services and to assess their level of functioning. METHOD: Non-inpatient services matching NSW Health's definition for high support, very high support and residential rehabilitation were sent a survey regarding type of service, criteria for acceptance, choice of housing options, patient demographics, evaluation methods and staff details. The Camberwell Assessment of Need was used to assess needs and the Life Skills Profile-16 was used to assess level of functioning. Comparisons were made between services operated by NSW Health and non-government organizations (NGOs), rural and urban services and services providing 24-hour support and those with less intensive staffing. RESULTS: Forty of the 42 identified services were included in the survey (95% response rate) of which 25 were operated by NGOs. There were 753 residential beds and 1132 patients lived in these facilities over the financial year 2001/2002. Interviews were completed at 25 locations across the state with 159 patients. Seventy-four percent were male and the mean age was 43 years. Patients had on average 7.6 needs of which 2.2 were unmet and their mean LSP-16 total score was 16.8. Almost half the patients responded that they were homeless at one time because they could not find appropriate housing. CONCLUSIONS: There were no significant differences in the number of needs expressed by patients residing in government or non-government operated services, those living in rural or urban areas and those in 24-hour services compared to patients in less intensively staffed services. Existing services are doing a good job of meeting patients' needs for practical assistance, but social and psychological needs remain unmet for a significant proportion.
Abstract: Cat odor elicits a profound defensive reaction in rats that is reduced by benzodiazepine drugs. The neural correlates of this phenomenon were investigated here using Fos immunohistochemistry. Rats received either midazolam (0.75 mg/kg, s.c.) or vehicle and were exposed to pieces of a collar that had been worn by a domestic cat or an unworn (dummy) collar. Cat odor caused midazolam-sensitive defensive behavioral responses, including avoidance of collar contact, inhibition of grooming, and prolonged rearing. Cat odor exposure induced Fos expression in the posterior accessory olfactory bulb (glomerular, mitral, and granule cell layers), with granule cell layer activation attenuated by midazolam. High basal Fos expression, and some cat odor-associated Fos expression, was evident in the main olfactory bulb (glomerular cell layer), and midazolam exerted a strong inhibitory effect in this region. Midazolam inhibited Fos expression in key limbic regions involved in pheromone transduction (medial amygdala and bed nucleus of the stria terminalis) and defensive behavior (prelimbic cortex, lateral septum, lateral and medial preoptic areas, and dorsal premammillary nucleus). However, midazolam failed to affect cat odor-related Fos expression in a range of key defense-related sites, including the ventromedial hypothalamic nucleus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and cuneiform nucleus. These results indicate that midazolam exerts a region-specific effect on the neural substrates activated by predator odor, with effects in the lateral septum and dorsal premammillary nucleus likely to be of major importance. These findings also suggest the intriguing hypothesis that cat odor is processed by rats as a "pheromone-like" stimulus.
Abstract: Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.
Abstract: Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 x 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.
Abstract: BACKGROUND: Gaining consumer feedback about nursing care and discharge planning is especially important given the changes that have occurred in acute inpatient mental health facilities. Consumers can best define the quality of the service they receive and surveys are considered to be good sources of information about nursing care and discharge planning. AIM: The aims of this study were to clarify consumer discharge needs, ascertain consumer perceptions of helpful practice, identify areas that require improvement, identify resources consumers deem important, ascertain satisfaction with specific aspects of services, and obtain baseline data to improve future discharge planning. METHOD: Satisfaction-with-services and discharge questionnaires were completed by clients (39 and 45, respectively) prior to discharge from three acute inpatient mental health units over a 2-month period. FINDINGS: Findings indicated that clients were most satisfied with the respect they received from staff, attention staff gave to concerns and worries, quality of service provided by nurses, way treatment met client needs and overall stay in hospital. The majority of respondents (95%) indicated that their discharge arrangements were explained to them and 90% were satisfied with these. Whilst over two-thirds indicated that the information provided in hospital to assist with discharge had been helpful, they highlighted some areas for service improvement. Resources to prepare them better for discharge included increased contact with consumer consultants and more information about mental health problems, medication and relapse prevention. CONCLUSION: This study constitutes another small step towards decreasing the gap between consumer expectations and actual treatment by asking consumers about their perceptions of discharge planning. The findings provide the basis for the development of more appropriate strategies to improve the continuity of services between hospital and community mental health settings.
Abstract: The oral and written presentation of work arising from clinical practice, service development, quality improvement projects and research is presently encouraged and supported. Because this work may involve consumers, staff and the organization, it is important that proper consideration is given to how the work is disseminated, including any ethical implications. There is a need to ensure that consumers, staff, facilities, the organization and intellectual property are protected from any potential concerns that may arise. This research note provides protocols and a checklist that may be of interest and may be relevant for clinicians and researchers to review and appraise their work before oral or written presentation.
Abstract: Male Wistar rats were treated with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") using either a high dose (4 x 5 mg/kg over 4 h) or low dose (1 x 5 mg/kg over 4 h) regimen on each of 2 consecutive days. After 10 weeks, rats were tested in the social interaction and emergence tests of anxiety. Rats previously given either of the MDMA dose regimens were significantly more anxious on both tests. After behavioral testing, and 3 months after the MDMA treatment, the rats were killed and their brains examined. Rats given the high-, but not the low-, dose MDMA treatment regimen exhibited significant loss of 5-hydroxytryptamine (5-HT) and 5-HIAA in the amygdala, hippocampus, striatum, and cortex. Quantitative autoradiography showed loss of SERT binding in cortical, hippocampal, thalamic, and hypothalamic sites with the high-dose MDMA regime, while low-dose MDMA only produced significant loss in the medial hypothalamus. Neither high- nor low-dose MDMA affected 5HT(1A) receptor density. High-dose MDMA increased 5HT(1B) receptor density in the nucleus accumbens and lateral septum but decreased binding in the globus pallidus, insular cortex and medial thalamus. Low-dose MDMA decreased 5HT(1B) receptor density in the hippocampus, globus pallidus, and medial thalamus. High-dose MDMA caused dramatic decreases in cortical, striatal, thalamic, and hypothalamic 5HT(2A)/(2C) receptor density, while low-dose MDMA tended to produce similar effects but only significantly in the piriform cortex. These data suggest that even brief, relatively low-dose MDMA exposure can produce significant, long-term changes in 5-HT receptor and transporter function and associated emotional behavior. Interestingly, long-term 5-HT depletion may not be necessary to produce lasting effects on anxiety-like behavior after low-dose MDMA.
Abstract: RATIONALE: There is some uncertainty whether the acute hyperthermia caused by MDMA (ecstasy) plays a significant role in determining the long-term neurotoxic effects on brain 5-HT systems and associated changes in mood and behaviour. OBJECTIVE: The present study assessed whether long-term behavioural and cognitive changes seen in MDMA-treated rats are affected by hyperthermia at the time of drug administration. METHOD: Male Wistar rats were treated with MDMA (4x5 mg/kg i.p. over 4 h on 2 consecutive days) or vehicle at either a high ambient temperature (28 degrees C) or a low ambient temperature (16 degrees C). Eight to 18 weeks later, rats were tested in behavioural measures of anxiety (social interaction and emergence tests), a test of cognition (object recognition test) and the forced swim test of depression. At the conclusion of behavioural testing the rats were killed and their brains analysed using HPLC. RESULTS: MDMA treatment caused a clear and consistent hyperthermia at 28 degrees C and hypothermia at 16 degrees C. Months later, rats pre-treated with MDMA at either 16 or 28 degrees C displayed increased anxiety in the social interaction and emergence tests and reduced escape attempts and increased immobility in the forced swim test. MDMA pre-treatment was also associated with poorer memory on the object recognition test, but only in rats given the drug at 28 degrees C. Rats pre-treated with MDMA showed loss of 5-HT in the hippocampus, striatum, amygdala and cortex, regardless of body temperature at the time of dosing. However, 5-HIAA loss in the amygdala and hippocampus was greater in rats pre-treated at 28 degrees C. Dopamine in the striatum was also depleted in rats given MDMA. CONCLUSIONS: These results indicate that hyperthermia at the time of dosing with MDMA is not necessary to produce subsequent 5-HT depletion and anxiety in rats. They also extend previous findings of long-term effects of brief exposure to MDMA in rats to include apparent "depressive" symptoms in the forced swim model.
Abstract: 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a drug frequently used under hot conditions in nightclubs. In rats tested in the social interaction paradigm, greater prosocial effects of MDMA (5.0 mg/kg) were seen at a hot temperature (30 degrees C) relative to normal laboratory temperature (21 degrees C). In the intravenous drug self-administration paradigm, hot temperature (30 degrees C) increased the number of MDMA infusions (0.1, 0.3 or 1.0 mg/kg/infusion) self-administered by rats. Hot temperatures thus appear to affect both the social and reinforcing effects of MDMA.
Abstract: Recent behavioral and pharmacological research shows extensive interplay between cannabinoid and opioid neurochemical systems. Here we examined the neuroanatomical basis of this interaction using c-fos immunohistochemistry. We compared Fos immunoreactivity in groups of male albino Wistar rats treated with vehicle, Delta(9)-tetrahydrocannabinol (THC, 10 mg/kg, i.p.), naloxone (10 mg/kg, i.p.) or THC and naloxone in combination. Locomotor activity was depressed in both THC treatment groups and moderately inhibited in rats given naloxone alone. Results showed that naloxone inhibited THC-induced Fos immunoreactivity in several key brain regions including the ventral tegmental area, ventromedial and dorsomedial hypothalamus, central caudate-putamen and ventrolateral periaqueductal grey. Conversely, naloxone and THC had an additive effect on Fos immunoreactivity in the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division), the insular cortex, and the paraventricular nucleus of the thalamus. These findings complement earlier pharmacological results showing potent modulation of cannabinoid-induced analgesia, appetite and reward by opioids. The inhibitory effects of naloxone on THC-induced ventral tegmentum, hypothalamic and periaqueductal grey Fos expression point to these structures as key sites involved in cannabinoid-opioid interactions.
Abstract: The long-term behavioural and neurotoxic effects of 3,4-methlyenedioxymethampthetamine (MDMA, "Ecstasy") were examined in rats. Rats were given MDMA (5 mg/kg i.p. once per hour for 4 h) or vehicle injections on each of two consecutive days at an ambient temparature of 28 degrees C. MDMA caused acute hyperthermia and locomotor hyperactivity on both days. Four and six weeks after drug administration the rats previously treated with MDMA showed elevated levels of anxiety-like behaviour in the emergence and social interaction tests, respectively. At 9 weeks post-MDMA, the rats displayed an increase in anxiety on the elevated plus-maze test relative to controls. Ten weeks following treatment the rats were killed and their brains dissected and neurotramitter content analysed using High Performance Liquid Chromotography (HPLC). Rats previously given MDMA showed significantly decreased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the amygdala, hippocampus and striatum relative to controls. This 5-HT depletion may have a causal role in producing increased anxiety-like behaviours in MDMA-treated rats. These results are consistent with human studies suggesting that exposure to high doses of MDMA may predispose to long-term psychological problems such as anxiety and depression.
Abstract: OBJECTIVE: To examine age, period and cohort effects on Australian suicide rates. METHOD: Male suicide rates for successive 5-year periods between 1919 and 1998, and for 1999 were displayed graphically to examine interactions between age, period and cohort effects. RESULTS: There has been a pronounced period effect on male suicide rates in all age groups over the last few decades, with lower rates in wartime and peak rates for most cohorts in the 1960s. Peak rates of all adult female 5-year age cohorts occurred in the 1960s or early 1970s. CONCLUSION: Most so-called cohort effects appear to be associated with environmental changes that may not be a function of the cohort itself. While much attention has focused on the rising suicide rates in young males in Australia, local media and health authorities have given little emphasis to the high rates found in elderly males.
Abstract: This prospective study examined the effect of medication compliance and substance abuse on 4 year outcome in 99 patients following a relapse of schizophrenia. Univariate survival analysis revealed longer community tenure in patients if they were over the age of 35 years, not admitted 2 years prior to the index episode, remained medication compliant and did not abuse substances during the follow-up interval. Comparisons between patients grouped according to medication compliance and current substance abuse indicated that those patients who regularly took their medication but also abused substances were readmitted to hospital sooner (median survival, 10 months) compared to compliant patients who did not use substances (37 months). For noncompliant patients, time to first readmission was shorter for patients with a dual diagnosis (5 months) compared to patients with a singular diagnosis of schizophrenia (10 months). Over the 4 year period, noncompliant patients with a dual diagnosis (n=28) accounted for 57% of all hospital readmissions for the cohort and averaged 1.5 admissions per patient year. These data indicate that much of the benefit that antipsychotic medication has on increasing community survival is reduced by substance abuse. This interval is further reduced in patients who are both substance abusers and noncompliant with medication resulting in a revolving door situation of frequent hospital admissions. Integrated treatment programs which address these issues are likely to reduce the need for hospital readmission in patients with a dual diagnosis.
Abstract: To help further identify the reward-relevant regions activated by electrical stimulation of the lateral hypothalamus, Fos expression was quantified in 23 brain regions in naïve, awake rats following non-contingent stimulation with a frequency that supports self-stimulation (100 Hz), a frequency that supports only minimal responding (50 Hz) and a frequency that does not support self-stimulation (25 Hz). Fos expression was also examined in stimulated and unstimulated rats pretreated with SCH 23390 (a dopamine D1 antagonist) or spiperone (a D2-like antagonist), at doses known to greatly inhibit responding for self-stimulation. Lowering the stimulation frequency from 100 to 50 Hz reduced Fos labelling in all areas, except for a few cells immediately surrounding the electrode tip. No differences were observed between unstimulated rats and those receiving 25 Hz stimulation. This suggests that a critical threshold of stimulation is required before other reward-relevant regions in the midbrain and forebrain are recruited with higher frequency stimulation. Pretreatment with SCH 23390 (0.1 mg/kg) inhibited stimulation-induced Fos expression in some key dopamine terminal areas, such as the nucleus accumbens (core and shell) and medial caudate-putamen, but not in directly driven neurons near the stimulation site. In contrast, spiperone (0.1 mg/kg) did not affect the pattern of stimulation-induced Fos expression, but induced immunolabelling in the dorsolateral caudate-putamen, an area associated with the extrapyramidal side-effects of antipsychotic drugs. These results reveal the utility of Fos immunohistochemistry to show how different treatments that alter the rewarding impact of electrical brain stimulation achieve their effects at the neural level.
Abstract: Previous studies have suggested that cannabis-like drugs produce mainly aversive and anxiogenic effects in Wistar strain rats, but rewarding effects in Lewis strain rats. In the present study we compared Fos expression, body temperature effects and behavioral effects elicited by the cannabinoid CB(1) receptor agonist CP 55,940 in Lewis and Wistar rats. Both a moderate (50 microg/kg) and a high (250 microg/kg) dose level were used. The 250 microg/kg dose caused locomotor suppression, hypothermia and catalepsy in both strains, but with a significantly greater effect in Wistar rats. The 50 microg/kg dose provoked moderate hypothermia and locomotor suppression but in Wistar rats only. CP 55,940 caused significant Fos immunoreactivity in 24 out of 33 brain regions examined. The most dense expression was seen in the paraventricular nucleus of the hypothalamus, the islands of Calleja, the lateral septum (ventral), the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division) and the ventrolateral periaqueductal gray. Despite having a similar distribution of CP 55,940-induced Fos expression, Lewis rats showed less overall Fos expression than Wistars in nearly every brain region counted. This held equally true for anxiety-related brain structures (e.g. central nucleus of the amygdala, periaqueductal gray and the paraventricular nucleus of the hypothalamus) and reward-related sites (nucleus accumbens and pedunculopontine tegmental nucleus). In a further experiment, Wistar rats and Lewis rats did not differ in the amount of Fos immunoreactivity produced by cocaine (15 mg/kg). These results indicate that Lewis rats are less sensitive to the behavioral, physiological and neural effects of cannabinoids. The exact mechanism underlying this subsensitivity requires further investigation.
Abstract: Male Wistar rats were administered either (a) a high dose regime of 3,4-methylenedioxymethamphetamine (MDMA) (4 x 5 mg/kg, i.p. over 4 h on each of 2 consecutive days), (b) a moderate dose regime of MDMA (1 x 5 mg/kg on each of 2 consecutive days), (c) D-amphetamine (4 x 1 mg/kg over 4 h on each of 2 days), or (d) vehicle injections. The high MDMA dose regime and the amphetamine treatment both produced acute hyperactivity and hyperthermia. Twelve weeks later, all rats were tested in the drug-free state on a battery of anxiety tests (elevated plus maze, emergence and social interaction tests). A further 2 weeks later they were tested on a novel object recognition memory task. Rats previously given the neurotoxic dose of MDMA showed greater anxiety-like behaviour on all three anxiety tests relative to both controls and D-amphetamine-treated rats. Rats given the moderate MDMA dose regime also showed increased anxiety-like behaviour on all three tests, although to a lesser extent than rats in the high dose group. In the object recognition task, rats given the high MDMA dose regime showed impaired memory relative to all other groups when tested at a 15-min delay but not at a 60-min delay. Rats previously exposed to amphetamine did not differ from saline controls in the anxiety or memory tests. These data suggest that moderate to heavy MDMA exposure over 48 h may lead to increased anxiety and memory impairment 3 months later, possibly through a neurotoxic effect on brain serotonin systems.
Abstract: Wistar rats were exposed to a fabric collar that had been worn by a domestic cat. Exposure took place in an open rectangular arena containing a small wooden "hide box". Rats exposed to cat odor spent more than 87% of their time in the hide box during a single 20-min exposure session, whereas rats exposed to a control odor (an unworn collar) spent less than 20% of their time hiding. One hour following this session, rats were killed and Fos immunoreactivity was compared between cat odor-exposed rats, control odor-exposed rats and an additional group that had remained in their home cages. Cat odor-exposed rats showed greater Fos expression than controls in many brain regions, particularly in the medial amygdala, medial hypothalamus and periaqueductal gray. Significant findings included strong and selective induction of Fos in the posteroventral medial amygdaloid nucleus, the premamillary nucleus (dorsal part), ventromedial hypothalamic nucleus (dorsomedial part), dorsomedial hypothalamic nucleus, periaqueductal gray (dorsomedial, dorsolateral and ventrolateral parts) and the cuneiform nucleus. Robust Fos expression in the ventromedial hypothalamus, premamillary nucleus and periaqueductal gray confirms previous suggestions of a role for these areas in predator-induced defensive behavior. Fos immunoreactivity in the medial, but not central or basolateral amygdala is a novel finding and draws attention to this subregion as a possible interface between olfactory input and emotional output.
Abstract: Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.
Abstract: A series of experiments examined various aspects of beer consumption in male Wistar rats. In the first experiment, rats were given home cage access to either beer or ethanol solutions under free access conditions. It was found that rats consumed greater amounts of moderate strength beer (2.7% ethanol by volume) or regular strength beer (5.0% ethanol) than equivalent dilute ethanol solutions in water. Consumption of 2.7% beer was greater than 5.0% beer and access to either beer, but not dilute ethanol, solutions caused substantial increases in total fluid intake per day. In the second experiment, individual rats given daily 30-min drink sessions consumed more 2.7% beer than 3.85% beer and more 3.85% than 5.0% beer. A "hangover" effect was evident after the first day of consumption of 5.0% beer with subsequent intake of this beer suppressed after high intake on first exposure. Intake of the low-strength beer approached intake of isocaloric (8.6%) sucrose solution. In a third experiment, a lick-based progressive ratio paradigm was implemented where rats had to emit progressively greater number of licks for a fixed volume (0.1 ml) of 2.7% beer or 8.6% sucrose. Using this paradigm, it was shown that food deprivation increased the motivation to consume beer and sucrose as shown by elevated break points (the highest ratio reached). Food deprivation also increased locomotor activity in the drinking environment. In contrast, cocaine (20 but not 10 mg/kg) caused a decrease in the break point for sucrose and beer, an effect probably mediated by the anorexic properties of the drug. It is concluded that rats will avidly consume beer, particularly of moderate alcohol content, but that such consumption may be mediated more by the nutritive and palatable characteristics of the beer rather than by the psychoactive effects of the alcohol it contains.
Abstract: Rats were injected with 3,4-methylenedioxymethamphetamine ("Ecstasy") and assessed for changes in locomotor activity and for the expression of the immediate early gene c-fos throughout the brain. A dose-dependent increase in locomotor activity was seen with 3,4-methylenedioxymethamphetamine (0, 5 and 20 mg/kg) that continued for at least 2 h following administration. Dose-dependent increases in c-fos expression were seen in much of the cortex, forebrain, brainstem and cerebellum in rats given 3,4-methylenedioxymethamphetamine. Expression was pronounced in 5-hydroxytryptamine terminal regions including the medial prefrontal cortex, caudate-putamen, nucleus accumbens, olfactory tubercle, islands of Calleja, lateral septum, paraventricular hypothalamus and paraventricular thalamus. High levels of c-fos expression were also seen in the supraoptic and median preoptic nuclei, regions involved in the control of fluid balance and body temperature, respectively. This is potentially important since deaths in 3,4-methylenedioxymethamphetamine users have been linked to hyperthermia and hyponatremia. In the brainstem, two regions of high c-fos expression were Barrington's nucleus, which is involved in micturition, and the pontine reticular nucleus oralis, a region involved in motor control of mastication. Activation of this latter structure may partly explain the bruxism (grinding of the jaw) reported by human 3,4-methylenedioxymethamphetamine users. Robust c-fos expression was seen in the cerebellum, particularly in the flocculus, and this may explain the reported deleterious effects of 3,4-methylenedioxymethamphetamine on balance and co-ordination. Significant c-fos expression was also seen in the ventral tegmental area, amidst the cell bodies of mesolimbic and mesocortical dopamine neurons, and in the median and dorsal raphe, where the serotonergic innervation of the forebrain originates. Double-labelling of fos-positive neurons with 5-hydroxytryptamine showed that only a small number of serotonergic neurons in the raphe expressed c-fos following 3,4-methylenedioxymethamphetamine. The widespread distribution of 3,4-methylenedioxymethamphetamine-induced c-fos expression seen in this study can be linked to the profound alterations in physiological function, mood and behaviour produced by this drug.
Abstract: Rats voluntarily consumed beer in a distinctive environment during 30 min daily sessions over 21 days, ingesting a daily average of 0.96 g/kg of ethanol. On a final test day, rats in a 'craving' condition were denied access to the beer in the drinking environment. The expression of c-fos in the brain of 'craving' rats was compared with that in rats given free access on the test day ('beer' condition), and to rats which had been repeatedly placed in the drinking environment without ever having access to beer ('control' condition). Rats in the 'craving' condition showed significantly higher c-fos counts than either the 'beer' or 'control' rats in a variety of corticolimbic and brainstem structures, indicating that activation of these regions occurs when a desirable alcoholic beverage is expected but not received.
Abstract: Rats were injected with the cannabinoid receptor agonists delta 9-THC (5 mg/kg) or anandamide (20 mg/kg) and assessed for changes in body temperature and locomotor activity. Their brains were then examined for the expression of the immediate early gene c-fos. Similar reductions in body temperature and locomotor activity were seen with delta 9-THC and anandamide although there was evidence, in line with previous reports, to suggest a shorter duration of action of anandamide. delta 9-THC and anandamide caused equally high levels of c-fos expression in the paraventricular nucleus of the hypothalamus and the lateral septum. Both drugs also increased c-fos expression in the central nucleus of the amygdala although the effect was greater with delta 9-THC. Only delta 9-THC caused significant increases in c-fos expression in the nucleus accumbens and caudate-putamen. These differences may be linked to differential activation of cannabinoid receptor subtypes or to differences in efficacy in activating second messenger systems linked to cannabinoid receptors. These findings complement evidence of qualitative differences in the actions of anandamide and delta 9-THC emerging from tests of drug discrimination, cross-tolerance, conditioned place preference and anxiety.
Abstract: Rats given cocaine (15 mg/kg, i.p.) every second day over a 2-week period displayed a progressively greater locomotor response to the drug over days indicating behavioral sensitization. When the cannabinoid receptor agonist CP 55,940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hyd roxypropyl)cyclohexanol) (10, 25 or 50 microg/kg) was administered under a similar regime, no such sensitization was observed. Rather, the two highest doses of CP 55,940 (25 and 50 microg/kg) caused locomotor suppression that lasted throughout administration. When rats pre-exposed 10 times to CP 55,940 were challenged with cocaine (15 mg/kg), no exaggerated locomotor response to cocaine was evident relative to non pre-exposed rats. When these rats were subsequently re-tested with CP 55,940, the cannabinoid continued to produce a dose-dependent suppression of locomotor activity. Finally, when CP 55,940 (50 microg/kg) was co-administered with cocaine, it significantly reduced the locomotor hyperactivity produced by the drug but did not block the development of behavioral sensitization. These results show that CP 55,940 does not sensitize locomotor activity with repeated administration in the same way as cocaine, and that pre-exposure or concurrent exposure to CP 55,940 does not enhance sensitivity to the subsequent behavioral effects of cocaine.
Abstract: In this study, c-fos immunohistochemistry was used to identify the brain regions activated by rewarding brain stimulation in rats. Rats had monopolar electrodes implanted in the medial forebrain bundle and were allocated to either a self-stimulation (n = 4), yoked stimulation (n = 4) or no stimulation (n = 6) group. In a single 1 h test session, each rat in the self-stimulation group made 1000 nose poke responses with each response followed by a 0.5 s train of brain stimulation. Rats in the yoked-stimulation group were paired with a partner in the self-stimulation group and received brain stimulation whenever their partner did. However, their nose poke responses did not trigger stimulation. This yoked procedure was thus used to identify any Fos-like immunoreactivity due to operant responding. Rats in the no stimulation group were placed in the same apparatus as the other rats but received no brain stimulation and were thus used to assess baseline Fos-like immunoreactivity. Results showed that stimulation increased Fos-like immunoreactivity in many areas of the brain in both the self-stimulation and yoked groups. The areas with the highest Fos-like immunoreactivity were ipsilateral to the electrode site and included the medial prefrontal cortex, lateral septum, nucleus accumbens (shell), the medial and lateral preoptic areas, bed nucleus of the stria terminalis, central amygdala, lateral habenula, dorsomedial hypothalamus, lateral hypothalamus and the anterior ventral tegmental area. Bilateral Fos-like immunoreactivity was evident in the nucleus accumbens core, paraventricular nucleus of the hypothalamus, the retrorubral fields and the locus coeruleus. A double-labelling procedure identifying both Fos and tyrosine hydroxylase was used to show that very few (< 5%) of the A10 dopamine cell bodies in the ventral tegmental area expressed Fos following brain stimulation. In contrast, most of the noradrenergic neurons of the locus coeruleus (A6), rubrospinal tract (A5) and pontine tegmental area (A7) were Fos positive. Overall, the results show that rewarding, brain stimulation induces Fos-like immunoreactivity in many forebrain regions but only sparsely in mesolimbic and mesocortical dopamine neurons. The similar patterns of Fos-like immunoreactivity seen in the self-stimulation and yoked-stimulation groups suggests that the operant responding for brain stimulation causes minimal Fos expression in itself.
Abstract: The pharmacokinetics of dexamethasone (DEX) were studied in 9 drug-free melancholically depressed patients and 10 healthy control subjects matched by sex and age. Each subject received 1 mg of DEX administered orally and by the (i.v.) route at 11:00 PM and serial blood samples were collected over the next 17 hours until 4:00 PM. There were no significant differences between the diagnostic groups and DEX bioavailability, peak plasma level, time to maximum concentration, or in elimination half-life after oral administration. Bioavailability estimates indicated that DEX absorption was incomplete and variable mean = 61%, SD = 14) in controls as well as depressed patients. In both groups there was a wide interindividual variability in plasma DEX levels following both oral and i.v. routes of administration. This variability could not be reliably predicted by differences in age, sex, or weight between subjects. The factors that accounted for most the variability in 4:00 PM plasma DEX levels after oral administration were clearance, bioavailability, and time to reach maximum concentration. Plasma DEX levels were lower in 3 depressed nonsuppressors compared to 3 matched controls who suppressed. No single pharmacokinetic factor was shown to be responsible for the lower DEX levels in the depressed nonsuppressors. These results indicate that plasma DEX levels need to be measured in each individual during the DST procedure so that this information may be taken into consideration when interpreting DST results.
Abstract: The effects of dopamine D1 and D2 agonists and antagonists on fixed-interval (FI) self-stimulation were investigated using a reward-summation model, trading off frequency with train duration. The D1 antagonist SCH 23390 (0.005-0.02 mg/kg) decreased FI self-stimulation and the inhibition was reversed by increasing stimulation frequency. Moreover, amphetamine (0.5 mg/kg) reversed the inhibition by a low dose of SCH 23390 (0.005 mg/kg) but not after a higher dose inhibition could not be dissociated from a performance deficit. There was no significant interaction between low doses of spiperone and SCH 23390 when coadministered that could not be predicted from their effects when given individually. Self-stimulation was inhibited by the D1 agonist SKF 38393 (5 mg/kg). When coadministered with amphetamine, SKF 38393 partially blocked amphetamine's facilitation. The D2 agonist bromocriptine (10 mg/kg) produced an extraordinary enhancement of performance that was also evident after a lower dose (5 mg/kg) when it was combined with amphetamine. This enhancement of performance showed little extinction when stimulation was no longer available, suggesting it was a novel form of stereotypy. These results support the concept that D1 dopamine receptors play a critical role in modulating the reinforcing consequences of lateral hypothalamic stimulation. The involvement of D2 receptors on reinforcement processes remains contentious due to their effects on performance and insensitivity of responding to coincide with changes in reinforcement magnitude.
Abstract: Three experiments investigated hypothalamic self-stimulation under a fixed-interval (FI) reinforcement schedule. An FI 20-s schedule was chosen to reduce stimulation density in order to minimize the influence of priming effects or stimulation aftereffects that can affect responding under other schedules of reinforcement. The first experiment showed that the influence of train duration is greatest at levels up to 1 s and thereafter level off over a wide range of train durations (1-32 s). The second experiment showed that altering frequency, current, or pulse width produced almost identical changes in FI responding. These findings show that the neutral network subserving hypothalamic self-stimulation simply integrates the amount of charge over time. It is relatively insensitive to the combination of stimulation parameters that make up a given waveform. In the third experiment, the chronaxies from the strength-duration curves indicate the neural substrate supporting self-stimulation has a great current-integrating capacity. Together, these experiments show that varying the amount of brain stimulation produce large and consistent changes in a number of FI response measures. These measures effectively describe different attributes of FI performance and include response rate, the postreinforcement pause, interresponse times of short duration and the temporal distribution of responses within the interval.
Abstract: Two models of reward summation were examined in 16 rats lever pressing for intracranial stimulation under fixed-interval (FI) reinforcement. The first model examined rate-frequency functions and the second model traded off frequency and train duration. The second model was selected to assess the effects of three drugs on reward summation. Both clonidine and pimozide inhibited FI self-stimulation, but pimozide's effect could not be distinguished from a performance deficit. Two amphetamine isomers facilitated self-stimulation in a manner suggesting enhanced reinforcement. The dextro isomer was four times more effective than the levo isomer to facilitate self-stimulation. This study shows that the combination of the FI schedule with a reward-summation model is well suited for evaluating the effects of drugs on self-stimulation. The advantages of this model are that inter-reinforcement intervals are separated, which minimizes priming and stimulation aftereffects, and more responding does not increase stimulation availability, thus eliminating rate-dependency effects.
Abstract: The aim of this study was to examine cortisol dynamics over a range of plasma dexamethasone (DEX) levels using a two-dose dexamethasone suppression test (DST). Two doses of DEX (0.5 and 1.5 mg) were administered in a randomized crossover design to 29 inpatients with major depression and 26 controls to identify the upper range of plasma DEX levels that would allow reliable interpretation of DST results. It was hypothesized that due to inappropriately high plasma DEX levels following 1.5 mg, several depressed patients would switch from suppressors after the 1.5 mg dose to nonsuppressors after 0.5 mg. In contrast, the nondepressed controls with high DEX levels following 1.5 mg would remain suppressors after the lower dose. Fourteen patients were identified as having high 4 p.m. DEX levels (greater than 4 nmol/l) after the 1.5 mg DST. Cortisol was suppressed in all of the subjects with high DEX levels. After 0.5 mg, five of the eight depressed patients with high DEX levels switched to nonsuppressors. In contrast, all six controls with high DEX levels remained suppressors. These results indicate that patients with high DEX levels after a 1 mg DST should be retested with a lower dose. This strategy enhances the sensitivity of the DST without loss of specificity.
Abstract: The aim of this study was to identify any relationships between various patient factors such as age, gender and concurrent medication that may affect plasma cortisol or dexamethasone (DEX) concentrations. Multiple regression analysis was used to formulate an equation to predict plasma DEX levels to identify factors that may influence DEX bioavailability. Pre- and post-DST cortisol levels did not increase with age, but DEX levels were higher in elderly depressed patients. Neither gender nor psychotropic medication affected plasma cortisol or DEX levels. There was no indication that pre-DST cortisol levels influenced plasma DEX levels to account for the lower DEX values in non-suppressors. Age was the only significant factor found in this study to influence DEX levels and it could be argued that the dose of DEX should be lowered when administering the DST to elderly patients to reduce plasma DEX variability.
Abstract: Two doses of dexamethasone (DEX) (0.5 and 1.0 mg) were administered in a randomized crossover design to 31 patients with major depression, 9 healthy controls, and 14 nondepressed psychiatric patients. Using this modified Dexamethasone Suppression Test (DST), minimum DEX levels of 6 nmol/liter at 8:00 AM and 2.0 nmol/liter at 4:00 PM were required to achieve reliable suppression of cortisol in healthy controls and nondepressed psychiatric patients. Failure to achieve these minimum plasma DEX levels was associated with similar rates of nonsuppression in both depressed and nondepressed patients, thereby reducing the specificity of the DST. Conversely, high DEX levels greater than 13 nmol/liter at 8:00 AM or 4.0 nmol/liter at 4:00 PM were associated with abnormal "suppressibility" in depressed patients, thereby reducing the sensitivity of the test. Controlling for plasma DEX concentrations by selecting a test result that fell within a plasma DEX window at 8:00 AM and 4:00 PM increased the sensitivity and specificity of the DST. Significant differences in plasma DEX between suppressors and nonsuppressors were no longer evident when comparing patients with adequate DEX levels, thus ensuring that cortisol escape reflected HPA axis changes associated with depression and not peripheral mechanisms responsible for the availability of DEX. These results suggest that the clinical utility of the DST would be significantly enhanced by extending the standard 1.0-mg DST and retesting those patients with levels outside the DEX window with a higher or lower dose. The data also indicate that the measurement of plasma DEX is essential to validly interpret DST status and highlight the need to standardize DEX assays to compare DST results between research centers.
Abstract: Plasma dexamethasone concentrations following oral dexamethasone administration were examined in 78 patients with major depression prior to and during treatment. The test-retest stability of plasma dexamethasone levels within patients was satisfactory with an overall significant positive correlation between tests for each patient. However, significant variability was noted in individual patients. Change in pre-DST cortisol and plasma dexamethasone levels were the two variables, in that order of importance, contributing to change in DST status. In studies examining the clinical utility of serial dexamethasone suppression tests as a guide to recovery from depression, the effect of variability in plasma dexamethasone concentrations should be taken into account.
Abstract: The mechanism by which choline accumulates in erythrocytes during treatment with lithium salts has been elucidated. A component of the study was a kinetic description of erythrocyte phospholipase-D, which catalyses the release of intracellular choline from phospholipids. Apparent steady-state kinetic parameters for calcium ions were determined: Km (+/- SD) = 0.6 +/- 0.3 mmol/l aqueous cell volume and Vmax (+/- SD) = 12 +/- 4 mumol/l packed red blood cells (RBC) min-1. Competitive inhibition of the phospholipase-D by barium ions was also observed. Other information concerning choline and lithium levels and red cell life-time was obtained from the literature. Details of the kinetics were used to develop a comprehensive dynamic model of choline metabolism by erythrocytes. The scheme is as follows; phosphatidylcholine associated with high density lipoproteins exchanges with the erythrocyte membrane phospholipids, the neutral phospholipids undergo two dimensional translational and rotational motion and also flip between each layer of the bilayer thus becoming exposed to an intracellularly-located phospholipase-D, whereupon the choline is hydrolysed and released into the intracellular milieu. A choline transport protein, which is able to be inhibited by lithium, mediates the influx and efflux of choline. The differential equations that describe reactant flux in this scheme were integrated numerically and the choline accumulation profiles under various conditions of transport and enzyme inhibition are presented. Computer solution of the model, by using as input values plasma lithium levels in the upper limit of the therapeutic range, required that the red cell life-time be reduced in order to explain the previously observed negative association between choline and increasing lithium levels. The results of the computer simulations under varying initial conditions of plasma and erythrocyte lithium and choline concentrations permit, for the first time, a comprehensive description of those factors affecting erythrocyte choline levels.
Abstract: The purpose of this study was to evaluate oral clonidine for testing growth hormone (GH) responsiveness in healthy adults. Oral clonidine (0.15 mg) produced a satisfactory GH response (greater than 4 ng/ml from basal) in eight out of 10 subjects, which is similar to rates reported after an equivalent intravenous dose. Elevated GH levels at baseline occurred in four out of five female subjects; this did not affect the clonidine-induced GH release. There were no significant differences at any time point in plasma prolactin or cortisol levels following clonidine, compared to placebo controls. Adequate plasma clonidine levels (greater than 0.4 ng/ml) were achieved in all subjects, with corresponding reductions in mean arterial blood pressure, but with only minimal adverse effects. Results from this study indicate that oral clonidine is a reliable method for testing GH responsiveness in adult subjects.
Abstract: Proton nuclear magnetic resonance (1H NMR) spectroscopy in conjunction with the inversion-recovery spin-echo pulse sequence was used to obtain spectra from rabbit brain homogenate. The instrumental parameters required for the acquisition of spectra together with the assignment of major peaks are given. The rationale and prospectus for the use of this technique for the study of neurochemistry is outlined.
Abstract: Detailed operating conditions are reported for the determination of choline in human erythrocytes using proton nuclear magnetic resonance spectroscopy in conjunction with the inversion-recovery spin-echo pulse sequence. The results of the NMR method were in excellent agreement with those obtained using an enzymatic (choline oxidase) assay; however, they were approximately three times higher than those reported using gas chromatography/mass spectrometry techniques. The differences may be partly due to the method of preparing or sampling cells since there is a distribution of choline in cells of different ages. However, choline levels were not affected by the methods used in the present study for storing or preparing cells.
Abstract: Red blood cell (RBC) choline and ergothioneine levels were measured after repeated sampling of bipolar manic-depressive patients over 11 months of lithium maintenance. In addition, blood levels were measured in healthy volunteers, newly hospitalised lithium-free patients and from patients prior to, and after, initiating lithium. RBC choline levels did not differ between normal volunteers and newly admitted lithium-free patients with either mania or depression. After 4 weeks of lithium treatment RBC choline levels increased 6-fold, whereas the levels of the closely related compound ergothioneine did not change. Significant changes in mood during lithium maintenance were not accompanied by changes in RBC choline levels. These data indicate that lithium produced a specific accumulation of choline in erythrocytes. However the increased levels appear to be unrelated to clinical state and do not distinguish lithium responders from non-responders
Abstract: Rats were given daily injections of choline, lithium or lithium plus choline for either 11 or 18 days and red cell choline, glycine and glutathione levels were measured using proton nuclear magnetic resonance spectroscopy. In addition, plasma choline, plasma lithium and red cell lithium levels were measured 4 hr after the last dosage. Choline (1 mmol/kg) alone increased plasma but not red cell choline concentrations. Lithium (0.94 mmol/kg) elevated red cell choline levels but did not affect plasma choline concentrations. In contrast, red cell choline levels were not elevated in rats treated with a higher dose of lithium (1.88 mmol/kg). When choline was given in addition to the lower dose of lithium, a similar accumulation of red cell choline was observed suggesting that the lithium-induced choline accumulation was not enhanced by a greater availability of free choline. No differences were detected in red cell glycine or glutathione levels between any of the treatment groups. Therefore, lithium produced a specific (dose-dependent) accumulation of choline in rat erythrocytes. However, the 100% increase observed in rats was not as marked as the increased red cell choline levels reported in patients maintained on lithium (8 to 10-fold). This discrepancy supports the concept that species differences exist in red cell choline transport or metabolism.
Abstract: Assessment of renal function was carried out in an unselected sample of patients with bipolar manic-depressive disorder receiving lithium for an average period of 4.5 years. Overall, glomerular filtration rate (GFR) fell within the established normal range based on sex and age, whereas measures of urinary concentrating ability were generally impaired. There was no relationship between duration of lithium treatment and either GFR or impairment of urinary concentrating ability. Moreover, there was no evidence of a progressive impairment of glomerular or tubular function in patients re-tested after 2 years. The results of this study confirm the safety of lithium administration in the majority of patients and emphasize the importance of careful clinical monitoring to avoid lithium intoxication.
Abstract: The first application of inversion-recovery spin-echo proton nuclear magnetic resonance spectroscopy to the monitoring of reactions in rat brain preparations is presented. The initial report of the assignment of proton spin-echo nuclear magnetic resonance spectra from rabbit brain homogenates (C. R. Middlehurst et al., J. Neurochem. 42, 878-879, 1984) was used to assist in the assignment of spectra acquired from rat brain homogenates that were obtained from animals killed by cervical fracture or focussed microwave irradiation. Microwave-irradiated brains were divided into four major anatomical regions. Differences in metabolite levels were detected when spectra from fresh tissue and from various regions were compared. The in situ steady-state kinetics of prolidase in whole brain homogenate was determined. The procedure relies on the spectral differences between enzyme substrates and reaction products. The concentration dependence of the rate of hydrolysis of glycyl-L-proline was discribable by the Michaelis-Menten expression with a Michaelis constant of 1.90 mmol L-1 and a maximal velocity of 9.30 mumol min-1 mg-1 protein. The reactions catalysed by glutaminase and acetylcholinesterase in the brain were also monitored.
Abstract: Equivalent oral dosages (800 mg, 21.6 mmol) of standard ( Lithicarb ) and sustained-release ( Priadel ) lithium carbonate preparations were administered using a randomised cross-over design to six patients receiving long-term lithium maintenance and eight healthy student volunteers. In both patients and students there were no significant differences between the two lithium preparations for plasma lithium level curves, bioavailability or total urinary excretion rates. There were no differences in peak lithium concentrations (C max) between the two preparations in both patients and students, although the times to maximal levels (T max) were delayed after Priadel in patients and volunteers. These data indicate that Priadel is a delayed-release rather than a true sustained-release preparation.
Abstract: Four experiments were conducted to elucidate the determinants of the initiation of and escape from electrical stimulation of the lateral hypothalamus under several different reinforcement schedules. The first experiment of this series used correlational and factor analytic techniques to show that, under continuous reinforcement, the vigour of initiation is determined more by forcement than by positive reinforcement. Forcement is defined as all of the performance changes directly elicited and potentiated by the stimulation. Escape is determined by adaptation of positive reinforcement, not by negative reinforcement or aversion. Continuous reinforcement schedules are, therefore, not appropriate for studying either the positive or negative reinforcement produced by brain stimulation. The second experiment used fixed-interval reinforcement schedules to eliminate the effects of forcement on initiation and adaptation of positive reinforcement on escape. Parametric manipulations indicate that activity in the positive reinforcement and escape systems is a simple function of stimulation charge. The combination of parameters which make up a given charge is of relatively little importance. However, the positive reinforcement system becomes maximally activated at far lower charges than does the escape system. The third experiment used a T-maze technique to show that, after 5 sec, anterior hypothalamic stimulation becomes negatively reinforcing, but posterior hypothalamic stimulation does not. Since the escape from posterior hypothalamic stimulation on a fixed-interval schedule can be dissociated from both negative reinforcement and adaptation of positive reinforcement, it is suggested that such escape is reinforced by a positive process triggered by the offset of stimulation (OFF positive reinforcement). The fourth experiment showed that stimulation trains longer than 10 sec are significantly less positively reinforcing than much shorter trains. This reduction in positive reinforcement confirms the development of negative reinforcement in long trains of hypothalamic stimulation, even at posterior electrodes. Negative reinforcement appears to be as general a property of hypothalamic stimulation as is positive reinforcement. Thus, depending on the reinforcement schedule and electrode site, the initiation of lateral hypothalamic stimulation may be determined by ON positive reinforcement, OFF positive reinforcement and forcement. Escape may be determined by OFF positive reinforcement, adaptation of positive reinforcement and negative reinforcement.(ABSTRACT TRUNCATED AT 400 WORDS)
Abstract: Equivalent oral dosages (800 mg, 21.6 mmol) of a standard (Lithicarb) and a sustained-release (Priadel) lithium carbonate preparation were administered to six patients receiving lithium maintenance treatment using a randomized cross-over design. There were no significant differences in the two preparations for 24 hour plasma level curves, 24 hour bioavailability, peak plasma concentrations (Cmax), time to peak plasma concentrations (Tmax) or urinary excretion rates. These results are in agreement with a previous study using Priadel in healthy volunteers, and indicate that Priadel is a delayed-release, rather than a true sustained-release preparation. In order to maintain therapeutic plasma levels and to minimise adverse effects that may occur with high plasma lithium levels, Priadel needs to be administered in divided dosages rather than as a single daily dose.
Abstract: The effects of negative energy balance on self-stimulation are a matter of considerable disagreement. This disagreement undoubtedly reflects the inadequacies of the continuous reinforcement self-stimulation procedures used in this type of experimentation. The present experiment uses a new fixed-interval reinforcement shuttle-box procedure which provides indices of reward and stimulation escape that are free from the numerous performance altering effects that confound continuous reinforcement performance. Whereas 24 h of food deprivation had no effect on stimulation initiation or escape rates, 48 h of food deprivation selectively increased initiation rates. The enhancement of reward was seen over virtually the entire anterior-posterior extent of the lateral hypothalamus and occurred irrespective of the occurrence of any stimulus-bound behaviors. Thus negative energy balance appears to selectively increase the excitability of reward-related neurons in the lateral hypothalamus. The self-stimulating rats became clearly hyperphagic, yet their weight gains were not significantly different from those of controls. The self-stimulation must, therefore, have greatly increased energy expenditure. Thus, not only does energy balance affect self-stimulation, but self-stimulation appears to affect energy balance.
Abstract: Families with a two-generational history of affective disorder and well and ill sibs were selected from a population of bipolar manic-depressive patients and typed for HLA antigens, blood groups, serum proteins and red cell enzymes. Segregation of specific HLA alleles was not associated with affective illness across family pedigrees. Further, no significant associations were found between affective disorder and ABO, Rh, MNSs blood groups or Hp, EsD, C3, Gc or PGM. Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.
Abstract: Psychiatric outpatients were assessed for dyskinetic movements using the abnormal involuntary movement scale (AIMS). The prevalence of tardive dyskinesia in an Australian sample of 66 patients was 44% which is similar to reported prevalence in other countries. Although the prevalence was significantly higher in patients over 45 years of age and with more than a 5 year history of neuroleptic medication, there were no significant correlations between presence of dyskinesias and age, sex or duration of neuroleptic treatment. Organic factors such as neurological disorders, ECT or alcoholism were not related to dyskinetic movements, nor was the use of anticholinergic or tricyclic antidepressant medication. The AIMS is a reliable rating scale for dyskinetic movements and could be used more widely as a screening instrument for early detection of tardive dyskinesia.
Abstract: It has been suggested that the tetracyclic antidepressant mianserin may be an antagonist at inhibitory presynaptic alpha-adrenoceptors. If mianserin exerted a selective antagonist effect it should produce effects that are essentially opposite to those of a selective agonist such as clonidine. This hypothesis was investigated in a shuttle-box self-stimulation model previously shown to be sensitive to alpha-adrenergic drugs. In this model a presynaptic alpha-adrenoceptor antagonist would be expected to enhance self-stimulation and to reverse the inhibitory effects of clonidine. Mianserin (2.5-4.0 mg/kg) did not enhance self-stimulation, but instead produced a selective inhibition of reward. Further, mianserin did not reverse the inhibitory effects of clonidine on self-stimulation. These data suggest that if mianserin is an antagonist of the presynaptic alpha-adrenoceptors it is not a selective antagonist. It is possible that the presynaptic alpha-adrenoceptor antagonism may be effects on postsynaptic alpha-adrenoceptors and/or on a presynaptic noradrenaline reuptake mechanism.
Abstract: Prolactin (PRL) levels in unmedicated male patients with acute schizophrenia were within normal range at baseline, increased five fold after a challenge dose of thioridazine, did not significantly increase further after therapeutic dosages, and remained elevated for the duration of treatment. The rise in PRL levels was significantly correlated with the steady-state plasma levels of thioridazine and/or mesoridazine. Baseline and challenge-dose PRL levels did not correlate with severity of symptoms as measured by the Brief Psychiatric Rating Scale, or predict response to thioridazine. Overall, there was a trend for the drug and PRL levels to increase very quickly and remain elevated while the clinical response was gradual over the four-week period. clinically, it may be useful monitoring PRL levels, since the therapeutic dosage should usually be above the dosage required to produce maximal PRL levels.
Abstract: The effects of dopamine agonists on self-stimulation are a matter of considerable dispute. Apomorphine has variously been reported to inhibit, have no effect on, or to facilitate lever-press self-stimulation. To investigate the possibility that these discrepancies may reflect peculiarities of the lever-press test situation, the present study investigated the effects of apomorphine on locomotor initiation of and escape from lateral hypothalamic stimulation in a shuttle-box. Apomorphine had relatively little effect on the initiation behavior, but it produced a large and dose-dependent inhibition of escape. These data suggest that apomorphine acts to inhibit the aversive component of lateral hypothalamic stimulation. The implications of these findings for the usefulness of the shuttle-box in investigating the pharmacology of self-stimulation are discussed.
Abstract: Onset of mania was evaluated retrospectively in 48 bipolar manic-depressive patients. Mania occurred as the initial episode in 40% of cases. In patients with initial episode of depression, approximately 80% developed mania prior to their third episodes of depression and within 5 years from the onset of this illness. Differences in type of illness onset were related to family history of bipolar illness and sex of the proband. Male patients with a positive family history were significantly more likely to manifest mania at onset of illness.
Abstract: The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors.
Abstract: An alpha-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the alpha-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral alpha-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an alpha-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission.
