Translational Studies on Early-life Stress and Vulnerability to Alcohol Addiction

早期生活压力和酒精成瘾脆弱性的转化研究

基本信息

批准号：
8730268
负责人：
JEFFREY L WEINER
金额：
$ 9.01万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8730268
关键词：
Address Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Animal Experimentation Animal Model Anxiety Behavior Behavioral Biological Chronic Collaborations Communities Complex Data Development Disease Dopamine Drug abuse Education and Outreach Ensure Fruit Glutamate Receptor Goals Grant Human Institutes Intervention Life Life Stress Light Link Longevity Mediating Mental Depression Modeling National Institute on Alcohol Abuse and Alcoholism Neurobiology Nucleus Accumbens Phenotype Pilot Projects Publishing Recording of previous events Research Research Infrastructure Research Personnel Research Project Grants Research Training Risk Risk Factors Rodent Rodent Model Science Signal Transduction Stress Structure Testing Translational Research Trauma Universities Work addiction adverse outcome alcohol research alcohol use disorder behavior test drinking behavior forest human subject interdisciplinary approach multidisciplinary neglect neurobehavioral neurobiological mechanism neurophysiology nonhuman primate novel postnatal pre-clinical preclinical study prenatal programs receptor function research study social success translational study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The major goal of this P01 is to leverage institutional strengths in human, non-human primate, and rodent alcohol research to conduct translational studies directed at understanding the complex relationships between early life stress and vulnerability to alcohol use disorders. This project will take advantage of a highly productive and successful translational alcohol research unit at WFHS that was recently established with NIAAA programmatic grant support. This research unit will employ multidisciplinary approaches to identify enduring behavioral and neurobiological consequences of early life stress, determine how these alterations contribute to excessive alcohol drinking behaviors, and test novel interventional strategies that may be effective at alleviating addiction vulnerability associated with early life stress. The overarching hypothesis is that early life stress results in long lastin behavioral alterations that contribute to an increased risk of alcohol addiction (with a focus on anxiety-like behaviors). It is also hypothesized that these behavioral alterations are mediated, in part, by dysregulatlon of dopamine signaling and glutamate receptor function and plasticity in the nucleus accumbens. Aspects of these hypotheses will be evaluated in human subjects with and without a history of early life stress and with well-established non-human primate and rodent models of early life stress. This P01 will employ a Center-like structure that will include highly integrated rodent, non-human primate, and human projects. An administrative core will provide the infrastructure and support needed to ensure the success of the research. This core will also actively promote new translational alcohol research through a pilot project program and create new translational research training and outreach activities related to the scientific goals f the P01. A major emphasis will be to promote scientific integration across projects to maximize the likelihood of proceeding from benchside discovery to novel treatment strategies for alcohol addiction.

描述（由申请人提供）：本 P01 的主要目标是利用人类、非人类灵长类动物和啮齿动物酒精研究方面的机构优势进行转化研究，旨在了解早期生活压力与酒精使用障碍脆弱性之间的复杂关系。该项目将利用高生产力和 WFHS 最近在 NIAAA 计划拨款支持下成功成立了转化酒精研究单位。该研究小组将采用多学科方法来识别早期生活压力的持久行为和神经生物学后果，确定这些改变如何导致过度饮酒行为，并测试可能有效减轻与早期生活压力相关的成瘾脆弱性的新颖干预策略。最重要的假设是，早期生活压力会导致持久的行为改变，从而导致酒精成瘾的风险增加（重点是类似焦虑的行为）。还假设这些行为改变是通过介导的部分原因是伏隔核中多巴胺信号传导和谷氨酸受体功能和可塑性的失调。这些假设的各个方面将在有或没有早期生活压力史的人类受试者以及成熟的非人类灵长类动物和啮齿动物早期生活压力模型中进行评估。这个 P01 将采用类似中心的结构，其中包括高度集成的啮齿动物、非人类灵长类动物和人类项目。行政核心将提供确保研究成功所需的基础设施和支持。该核心还将通过试点项目计划积极促进新的转化酒精研究，并创建与 P01 科学目标相关的新转化研究培训和推广活动。主要重点是促进跨项目的科学整合，以最大限度地提高从实验室发现到酒精成瘾新治疗策略的可能性。