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Role of Endocannabinoid System in Depressive Behavior

内源性大麻素系统在抑郁行为中的作用

基本信息

批准号：
9150671
负责人：
VINOD K YARAGUDRI
金额：
$ 20.22万
依托单位：
NATHAN S. KLINE INSTITUTE FOR PSYCH RES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-25 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9150671
关键词：
2-arachidonylglycerol Acute Adrenal Glands Animal Model Antidepressive Agents Autopsy Behavior Biological Brain Brain-Derived Neurotrophic Factor CNR1 gene Chronic Chronic stress Complex Corticosterone Data Depressive disorder Development Disease Drug Targeting Endocannabinoids Environmental Risk Factor Enzymes Epigenetic Process Etiology Female Functional disorder Gender Genetic Genetic Models Glycerol Goals Health Histone Acetylation Histones Human Hypothalamic structure Inbred WKY Rats Lipase Lysine Major Depressive Disorder Mediating Mental Depression Mental disorders Modeling Molecular Mood Disorders Moods Neurobiology Neurons Patients Pharmaceutical Preparations Pharmacotherapy Phenotype Pituitary Gland Play Prevalence Public Health Rattus Risk Rodent Model Role Seminal Serum Signal Transduction Societies Stress Sucrose Suicide Symptoms Testing Therapeutic Agents United States Variant Wistar Rats Woman accomplished suicide anandamide base brain tissue depressed patient depressive behavior depressive symptoms disability economic cost effective therapy emotional behavior endocannabinoid signaling endogenous cannabinoid system fatty acid amide hydrolase frontal lobe gender difference insight male men mood regulation mortality neuroadaptation neurotrophic factor personalized medicine personalized pharmacotherapy preference receptor upregulation relating to nervous system response sexual dimorphism social therapeutic target trait treatment response

项目摘要

DESCRIPTION (provided by applicant): Stress and depression related behaviors incur enormous social and economic costs, and are major leading causes of suicide worldwide. Currently available pharmacotherapies for depression are moderately effective, and that emphasizes the need to further our understanding of the neurobiology of depression and to develop effective pharmacotherapy. Depressive disorder is a complex and multifactorial trait with genetic and environmental contributing factors. Intriguingly, prevalence of depression is greater in women than men. However, the biological basis for this sexual dimorphism is not clearly understood. Recent studies have suggested a potential role for the endocannabinoid (eCB) system in mediating mood and emotional behaviors. However, the role of eCB system in depressive behavior is yet to be clearly understood. In this study, we will determine if there are any gender- specific differences in the components of eCB system associated with depressive behavior using stress (Wistar rat), and genetic (Wistar Kyoto rat) models and in postmortem brains of patients with major depression. We will further evaluate if drugs targeted to eCB system exert antidepressant-like effects in rodent models. The proposed studies would provide new insight/s into the role of eCB system in neurobiology of depression that might assist in the development of effective and personalized pharmacotherapy.

描述（由申请人提供）：压力和抑郁相关的行为产生巨大的社会和经济成本，是全球自杀的主要原因。目前可用的药物治疗抑郁症是适度有效的，这强调了我们需要进一步了解抑郁症的神经生物学，并开发有效的药物治疗。抑郁症是一种复杂的多因素特征，有遗传和环境因素的影响。有趣的是，女性抑郁症的患病率高于男性。然而，这种两性异形的生物学基础还不清楚。最近的研究表明，内源性大麻素（eCB）系统在介导情绪和情绪行为中的潜在作用。然而，eCB系统在抑郁行为中的作用尚未被清楚地了解。在这项研究中，我们将确定是否有任何性别特异性的差异，在eCB系统的组成部分与抑郁行为使用压力（Wistar大鼠），和遗传（Wistar京都大鼠）模型和在死后的大脑中的重度抑郁症患者。我们将进一步评估靶向eCB系统的药物是否在啮齿动物模型中发挥抗抑郁样作用。拟议的研究将为eCB系统在抑郁症神经生物学中的作用提供新的见解，这可能有助于开发有效和个性化的药物治疗。