STRESS AND ETHANOL SELF-ADMINISTRATION IN MONKEYS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 压力被认为是滥用乙醇的一个病因。然而，压力在过度饮酒风险中的作用很难从过度饮酒的压力中解脱出来。一个出发点是操作上定义的压力激活下丘脑-垂体-肾上腺（HPA）轴通过可测量的变化，促肾上腺皮质激素（ACTH）从垂体和皮质醇从肾上腺的循环水平。猴子在HPA轴对压力事件的内分泌反应方面表现出明显的个体差异，并且在它们选择自我给药的乙醇量方面也表现出明显的个体差异。为了解决的因果关系的相互作用的压力和过量的乙醇的相互作用，我们建议的特点HPA反应的压力之前，期间和之后的慢性乙醇自我管理的个体差异。此外，内分泌对压力的反应的本质使信息流、整合和功能输出的神经回路概念成为焦点。将HPA反应视为行为的中间决定因素，引导了转化奋进进入中间表型或“内表型”的领域。为了解决HPA反应作为过度乙醇自我给药风险的内在表型的预测有效性，我们将筛选大量猴的特异性HPA反应。将在乙醇自我给药程序中表征潜在内在表型群体分布极端的个体。最后，我们将筛选基因多态性，以确定那些与HPA应答内表型相关的基因多态性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stress is believed to be an etiological factor in the abuse of ethanol. However, the role of stress in the risk for excessive ethanol consumption is difficult to untangle from the stress derived from excessively drinking alcohol. A starting point is to operationally define stress as activation of the hypothalamic-pituitary-adrenal (HPA) axis through measurable changes in circulating levels of the hormones adrenocorticotropin (ACTH) from the pituitary and cortisol from the adrenals. Monkeys show clear individual differences in endocrine response of the HPA axis to stressful events and also clear individual differences in the amount of ethanol they choose to self-administer. To address the causal interaction of stress and excessive ethanol interaction, we propose to characterize individual differences in HPA response to stress prior to, during and following chronic ethanol self administration. Further, the very nature of endocrine response to stress brings into focus the concept of neurocircuitries underlying information flow, integration and functional output. Viewing the HPA response as an intermediate determinant of behavior guides a translational endeavor into the realm of intermediate phenotypes or "endophenotypes". To address the predictive validity of an HPA response as an endophenotype underlying the risk of excessive ethanol self-administration, we will screen a large population of monkeys for specific HPA responses. Individuals that are on the extreme ends of the population distribution of the potential endophenotype will be characterized in the ethanol self-administration procedure. Finally, we will screen gene polymorphisms to identify those associated with an HPA response endophenotype.Finally, we will screen gene polymorphisms to identify those associated with an HPA response endophenotype.