ADMINISTRATIVE CORE

行政核心

• 批准号: 8285312
• 负责人: JEFFREY L WEINER
• 金额: $ 12.39万
• 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/8285312
• 关键词: Address; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Anxiety; Awareness; Behavior; Behavioral; Behavioral Mechanisms; Complement; Complex; Dopamine; Education and Outreach; Ensure; Etiology; Faculty; Funding; Glutamate Receptor; Goals; Grant; Health Personnel; Human; Institutes; Institution; Instruction; Intervention; Leadership; Life Stress; Light; Link; Mediating; Medical center; Modeling; Monkeys; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Nucleus Accumbens; Phenotype; Pilot Projects; Postdoctoral Fellow; Public Health; Recording of previous events; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Training; Risk; Rodent; Rodent Model; Signal Transduction; Stress; Structure; Students; Training; Training Activity; Training Programs; Translational Research; Triad Acrylic Resin; addiction; alcohol research; alcohol use disorder; behavior test; drinking behavior; forest; human subject; innovation; insight; interdisciplinary approach; medical schools; multidisciplinary; neurobiological mechanism; nonhuman primate; novel; outreach; programs; receptor function; success; translational study; treatment strategy

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/

P01的主要目标是利用人类、非人类灵长类和啮齿动物的机构优势 酒精研究进行跨性别研究，旨在了解复杂的重新关系 在早年的生活压力和酒精使用障碍的脆弱性之间。该项目将利用 WFHS最近成立的五个高产量和成功的转化醇研究单位 在NIAAA方案赠款的支持下。该研究单位将采用多学科方法来 确定早期生活压力的持久的行为和神经生物学后果，确定这些 改变导致过度饮酒行为，并测试新的干预策略 可能在缓解与早期生活压力相关的成瘾易感性方面有效。最重要的是 假说是，早期生活压力会导致长期的行为改变，这有助于增加 酒精成瘾的风险(重点是焦虑类行为)。还假设这些行为 改变的部分原因是多巴胺信号和谷氨酸受体功能的失调。 以及伏隔核的可塑性。这些假设的各个方面将在人类受试者身上进行评估。 有或没有早期生活压力史，以及有良好的非人类灵长类和啮齿动物 早期生活压力的模型。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。行政核心将提供基础设施和 确保研究成功所需的支持。这一核心还将积极推动新的翻译 通过试点项目方案进行酒精研究，并创建新的翻译研究、培训和推广 与P01的科学目标有关的活动。一个主要的重点将是促进科学积分 跨项目，以最大限度地提高从替补发现到新治疗的可能性 酒精成瘾的策略。 相关性(请参阅说明)： 这项研究与公共卫生的相关性：拟议的研究涉及多学科、翻译 将把人类、非人类灵长类和啮齿动物酒精研究人员聚集在一起的研究倡议 解决有关连接早期生命的神经生物学机制的复杂和悬而未决的问题 压力和酒精成瘾。这些翻译研究将为重要的行为研究提供新的线索 表型与早期环境应激有关，与过度饮酒有关， 以及特定的神经生物学机制，这些机制可能是这些关系的基础。该项目还将探索 新的干预策略，可能会减轻与早年相关的成瘾脆弱性增加 生活压力。 项目/绩效现场(S)(如果需要额外空间，请使用项目/