BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。大量摄入酒精的历史似乎与人类冲动测量的增加有关。然而，人类受试者的研究一直无法区分之前的冲动基线测量和大量酒精消耗史的结果影响。 我们的食蟹猴酒精自我给药模型为酒精滥用提供了一个独特而重要的模型，并反映了在人类种群中注意到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项目的主要焦点是使用猴子模型来表征与过量酒精自我给药相关的遗传因素的两个方面的冲动(快速停止或抑制、反应和对延迟强化的厌恶)的前后测量。 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个月的慢性酒精自我管理；(2)确定慢性酒精自我管理是否增加了冲动测量；以及(3)确定与长期饮酒前后的冲动行为相关的大脑区域(眼眶内侧前额叶皮质)的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.