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

• 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
• 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

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。这个项目将利用一个高度生产和