BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目旨在了解过度饮酒风险的个体差异，重点关注冲动行为。大量乙醇摄入的历史似乎与人类冲动性的增加有关。然而，人类受试者研究无法区分先前的冲动基线测量与大量乙醇消费史的后果影响。 我们的食蟹猴自我给药乙醇模型提供了一种独特且重要的酒精滥用模型，并反映了人群中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，这些研究可以成为通过功能基因组学将乙醇影响的候选机制转化为人类状况的关键一步。 因此，我们这个 PARC 项目的主要重点是使用猴子模型来描述冲动性两个方面的前因和后果测量（快速停止或抑制反应的能力和对延迟强化的厌恶）与过度乙醇自我施用相关的遗传因素。 我们的具体目标是： (1) 确定酒精暴露前的冲动测量是否可以预测 12 个月内的长期自我饮酒； (2) 确定长期自我服用乙醇是否会增加冲动程度； (3) 确定长期饮酒前后与冲动行为（眼眶内侧前额叶皮层）相关的大脑区域中关键基因网络的表达。

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.