Autoradiographic localization of [delta] opioid receptors in the rat brain using a highly selective bis-penicillamine cyclic enkephalin analog

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25669/1/0000221.pd

The general social survey-national death index: an innovative new dataset for the social sciences

<p>Abstract</p> <p>Background</p> <p>Social epidemiology seeks in part to understand how social factors--ideas, beliefs, attitudes, actions, and social connections--influence health. However, national health datasets have not kept up with the evolving needs of this cutting-edge area in public health. Sociological datasets that do contain such information, in turn, provide limited health information.</p> <p>Findings</p> <p>Our team has prospectively linked three decades of General Social Survey data to mortality information through 2008 via the National Death Index. In this paper, we describe the sample, the core elements of the dataset, and analytical considerations.</p> <p>Conclusions</p> <p>The General Social Survey-National Death Index (GSS-NDI), to be released publicly in October 2011, will help shape the future of social epidemiology and other frontier areas of public health research.</p

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.

RATIONALE: Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. METHODS: Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. RESULTS: During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Collaborative planning approach to inform the implementation of a healthcare manager intervention for hispanics with serious mental illness: a study protocol

Background: This study describes a collaborative planning approach that blends principles of community-based participatory research (CBPR) and intervention mapping to modify a healthcare manager intervention to a new patient population and provider group and to assess the feasibility and acceptability of this modified intervention to improve the physical health of Hispanics with serious mental illness (SMI) and at risk for cardiovascular disease (CVD). Methods: The proposed study uses a multiphase approach that applies CBPR principles and intervention-mapping steps--an intervention-planning approach--to move from intervention planning to pilot testing. In phase I, a community advisory board composed of researchers and stakeholders will be assembled to learn and review the intervention and make initial modifications. Phase II uses a combination of qualitative methods--patient focus groups and stakeholder interviews--to ensure that the modifications are acceptable to all stakeholders. Phase III uses results from phase II to further modify the intervention, develop an implementation plan, and train two care managers on the modified intervention. Phase IV consists of a 12-month open pilot study (N = 30) to assess the feasibility and acceptability of the modified intervention and explore its initial effects. Lastly, phase V consists of analysis of pilot study data and preparation for future funding to develop a more rigorous evaluation of the modified intervention. Discussion: The proposed study is one of the few projects to date to focus on improving the physical health of Hispanics with SMI and at risk for CVD by using a collaborative planning approach to enhance the transportability and use of a promising healthcare manager intervention. This study illustrates how blending health-disparities research and implementation science can help reduce the disproportionate burden of medical illness in a vulnerable population

Transdisciplinary qualities in practice doctorates

Doctoral programmes in which candidates research their own practice can be characterised as having transdisciplinary (TD) qualities. While most of the emphasis in the literature and in policy on TD is on research in teams, we argue for an expansion of the scope in the conception and understanding of TD research to include the way it can be articulated and assessed in practice-led and practice-based doctorates. In this sense, it is worth exploring instances of doctoral programmes that potentially allow doctoral researchers to undertake projects that have TD qualities. In these doctoral projects, researchers draw from a variety of perspectives, for example from their work practices, the theorisation of those practices, experiential learning, multiple disciplinary knowledge and approaches as well as communications and networking with appropriate stakeholders. Drawing from previous scholarship of TD in other fields we analyse and evaluate the TD qualities of a particular doctoral programme. This analysis reveals a set of qualities recognised by the literature as TD and relevant to doctoral researchers: Researching collaboratively with stakeholders; Diversity of disciplinary expertise and assessment criteria; Integration of different methodologies; Situating the research in multiple contexts; Impact on the ‘situation’ through novel procedures or products; Ethics and the importance of trust; Reflection/reflexivity. The paper posits a convergence between practice doctorates and TD research and demonstrates how TD qualities help doctoral candidates to situate their research at the interface between academia and their professional work and develop projects that have creative and beneficial relevance for practice

Differential Cerebral Cortex Transcriptomes of Baboon Neonates Consuming Moderate and High Docosahexaenoic Acid Formulas

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system (CNS). These nutrients are present in most infant formulas at modest levels, intended to support visual and neural development. There are no investigations in primates of the biological consequences of dietary DHA at levels above those present in formulas but within normal breastmilk levels. METHODS AND FINDINGS: Twelve baboons were divided into three formula groups: Control, with no DHA-ARA; “L”, LCPUFA, with 0.33%DHA-0.67%ARA; “L3”, LCPUFA, with 1.00%DHA-0.67%ARA. All the samples are from the precentral gyrus of cerebral cortex brain regions. At 12 weeks of age, changes in gene expression were detected in 1,108 of 54,000 probe sets (2.05%), with most showing <2-fold change. Gene ontology analysis assigns them to diverse biological functions, notably lipid metabolism and transport, G-protein and signal transduction, development, visual perception, cytoskeleton, peptidases, stress response, transcription regulation, and 400 transcripts having no defined function. PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only LCPUFA biosynthetic enzyme that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated by high DHA, while the mitochondrial proton carrier, UCP2, was upregulated. TIMM8A, also known as deafness/dystonia peptide 1, was among several differentially expressed neural development genes. LUM and TIMP3, associated with corneal structure and age-related macular degeneration, respectively, were among visual perception genes influenced by LCPUFA. TIA1, a silencer of COX2 gene translation, is upregulated by high DHA. Ingenuity pathway analysis identified a highly significant nervous system network, with epidermal growth factor receptor (EGFR) as the outstanding interaction partner. CONCLUSIONS: These data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across a wide array of processes, in addition to changes in visual and neural function normally associated with formula LCPUFA