ADMINISTRATIVE CORE

本P01的主要目标是利用人类、非人灵长类动物和啮齿类动物的机构优势 酒精研究，以进行旨在了解复杂的相关性的实验性研究 早期生活压力和酒精使用障碍之间的联系。该项目将利用 最近在WFHS成立了一个高产和成功的转化酒精研究单位 在NIAAA的资助下该研究单位将采用多学科方法， 确定早期生活压力的持久行为和神经生物学后果，确定这些后果是如何产生的。 改变导致过度饮酒行为，并测试新的干预策略， 可能有效缓解与早期生活压力相关的成瘾脆弱性。总体 一种假设是，早期生活压力导致长期持续的行为改变， 酒精成瘾的风险（重点是焦虑样行为）。也有人假设，这些行为 这种改变部分是由多巴胺信号传导和谷氨酸受体功能失调介导的 和可塑性。这些假设的各个方面将在人类受试者中进行评估 有和没有早期生活压力史，以及有公认的非人灵长类动物和啮齿类动物 早期生活压力的模型。该P01将采用类似中心的结构，包括高度集成的 啮齿动物、非人类灵长类动物和人类项目。一个行政核心将提供基础设施， 确保研究成功所需的支持。这一核心也将积极推动新的翻译 通过试点项目计划进行酒精研究，并创建新的转化研究培训和推广 与P01的科学目标相关的活动。一个主要的重点将是促进科学整合 跨项目，以最大限度地提高从实验室发现到新型治疗的可能性 酒精成瘾的策略。 相关性（参见说明）： 本研究与公共卫生的相关性：拟议的研究是一个多学科的，翻译的， 该研究计划将汇集人类，非人类灵长类动物和啮齿动物酒精研究人员， 解决与早期生活有关的神经生物学机制的复杂和未解决的问题 压力和酒精成瘾。这些转化研究将为重要的行为学提供新的视角。 与早期环境压力相关的表型，它们与过量饮酒的关系， 以及可能构成这些关系基础的特定神经生物学机制。该项目还将探索 新的干预策略，可以减轻与早期- 生活压力 项目/施工现场（如果需要额外空间，请使用项目/施工现场）

The major goal of this P01 is to leverage institutional strengths in human, non-human primate, and rodent alcohol research to conduct translafional studies directed at understanding the complex relafionships between eariy life stress and vulnerability to alcohol use disorders. This project will take advantage of a highly producfive 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 eariy 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 eariy life stress. The overarching hypothesis is that eariy life stress results in long lasting 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 dysregulation 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 eariy life stress and with well-established non-human primate and rodent models of eariy 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 activifies related to the scientific goals of the P01. A major emphasis will be to promote scientific integrafion across projects to maximize the likelihood of proceeding from benchside discovery to novel treatment strategies for alcohol addiction. RELEVANCE (See instructions): Relevance of this Research to Public Health: The proposed studies oufiine a multidisciplinary, translational research initiative that will bring together human, non-human primate, and rodent alcohol researchers to address complex and unresolved questions regarding the neurobiological mechanisms that link eariy life stress and alcohol addiction. These translational studies will shed new light on important behavioral phenotypes associated with eariy environmental stress, their association with excessive alcohol drinking, and specific neurobiological mechanisms that may underiie these relationships. This project will also explore novel interventional strategies that may mitigate the increased addicfion vulnerability associated with eariy- life stress. PROJECT/PERFORIViANCE SITE(S) (if additional space is needed, use Project/