BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION

酒精神经适应的行为基因组学

• 批准号: 8357785
• 负责人: KATHLEEN A GRANT
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357785
• 关键词: Alcohol abuse; Alcohol consumption; Alcohols; Area; Brain; CCL18 gene; Chronic; Ethanol; Funding; Genes; Genetic; Grant; Heavy Drinking; Human; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Macaca fascicularis; Measures; Medial; Modeling; Monkeys; National Center for Research Resources; Population; Prefrontal Cortex; Primates; Principal Investigator; Psychological reinforcement; Recording of previous events; Research; Research Infrastructure; Resources; Risk; Self Administration; Source; Translating; United States National Institutes of Health; Variant; alcohol effect; alcohol exposure; behavioral genomics; chronic alcohol ingestion; cost; functional genomics; human subject; neuroadaptation; nonhuman primate; Alcohol abuse; Alcohol consumption; Alcohols; Area; Brain; CCL18 gene; Chronic; Ethanol; Funding; Genes; Genetic; Grant; Heavy Drinking; Human; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Macaca fascicularis; Measures; Medial; Modeling; Monkeys; National Center for Research Resources; Population; Prefrontal Cortex; Primates; Principal Investigator; Psychological reinforcement; Recording of previous events; Research; Research Infrastructure; Resources; Risk; Self Administration; Source; Translating; United States National Institutes of Health; Variant; alcohol effect; alcohol exposure; behavioral genomics; chronic alcohol ingestion; cost; functional genomics; human subject; neuroadaptation; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project aims at understanding individual variation in risk for excessive drinking, with a focus on impulsive behaviors. A history of heavy ethanol intake appears to be related to increases in measures of impulsivity in humans. However human subject studies have been unable to distinguish antecedent baseline measures of impulsivity from the consequential effects of a history of heavy ethanol consumption. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse, and reflects the individual differences in propensity to drink alcohol noted in the human population. Because of genetic similarities between humans and non-human primates, these studies can then be a key step in translating candidate mechanisms of ethanol's effects into the human condition through functional genomics. Thus, our primary focus of this PARC project is to use the monkey model to characterize antecedent and consequent measures of two aspects of impulsivity (the ability to rapidly stop, or withhold, responding and the aversion to a delay in reinforcement) with genetic factors related to excessive ethanol self-administration. Our Specific Aims are: (1) To determine if measures of impulsivity prior to alcohol exposure will predict chronic alcohol self-administration over a 12 month period; (2) To determine if chronic ethanol self-administration increases measures of impulsivity; and (3) To determine the expression of key gene networks in a brain area related to impulsive behaviors (the orbital medial prefrontal cortex) both prior to and following chronic alcohol drinking.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该项目旨在了解过度饮酒风险的个人变化，重点是冲动行为。沉重乙醇摄入量的史似乎与人类冲动性量度的增加有关。但是，人类学科的研究无法将冲动性的先前基线测量与大量乙醇消耗史的相应影响区分开。 我们在Cynomolgus Monkeys中乙醇自我给药的模型提供了一种独特而重要的酒精滥用模型，并反映了人口中引用的饮酒倾向的个体差异。由于人类和非人类灵长类动物之间的遗传相似性，这些研究可能是通过功能基因组学将乙醇作用的候选机理转化为人类状况的关键步骤。 因此，我们该PARC项目的主要重点是使用猴子模型来表征冲动性的两个方面的先行和随之而来的措施（快速停止或扣留，反应和对加强延迟的厌恶的能力）与遗传因素与过度乙醇相关的遗传因素。 我们的具体目的是：（1）确定在酒精暴露前的冲动度度量是否会预测在12个月内的慢性酒精自我管理； （2）确定慢性乙醇自我给药是否会增加冲动的度量； （3）在长期饮酒之前和之后，确定与脉冲行为（轨道内侧前额叶皮层）有关的大脑区域中关键基因网络的表达。