STRESS AND ETHANOL SELF-ADMINISTRATION IN MONKEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 压力被认为是滥用乙醇的一个病因因素。然而，压力在过度饮酒风险中的作用很难从过度饮酒产生的压力中解脱出来。从手术角度出发，应激定义为通过脑下垂体促肾上腺皮质激素(ACTH)和肾上腺皮质醇循环水平的可测量变化来激活下丘脑-垂体-肾上腺(HPA)轴。猴子在HPA轴对应激事件的内分泌反应上表现出明显的个体差异，在它们选择自我管理的酒精含量上也表现出明显的个体差异。为了解决压力和过量酒精相互作用的因果关系，我们建议表征慢性酒精自身给药之前、期间和之后HPA对应激反应的个体差异。此外，内分泌对应激反应的本质使信息流、整合和功能输出背后的神经回路的概念成为焦点。将HPA反应视为行为的中间决定因素会引导翻译努力进入中间表型或“内表型”的领域。为了解决HPA反应作为过量乙醇自我给药风险潜在内表型的预测有效性，我们将对大量猴子进行特定HPA反应的筛查。处于潜在内表型的种群分布两端的个体将在乙醇自我给药程序中被表征。最后，我们将筛选与HPA反应内表型相关的基因多态。

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.