STRESS AND ETHANOL SELF-ADMINISTRATION IN MONKEYS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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。为了解决压力和过量乙醇相互作用的因果关系，我们提出了表征HPA应激反应的个体差异之前，期间和之后的慢性乙醇自我管理。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，我们筛选了大量猴的特异性HPA反应。在乙醇自我给药程序中，对潜在内在表型的群体分布的极端个体进行了表征。基因多态性，以确定那些与HPA反应内表型正在进行中。

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. 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 proposed 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 have screened a large population of monkeys for specific HPA responses. Individuals on the extreme ends of the population distribution of the potential endophenotype were characterized in the ethanol self-administration procedure. Gene polymorphisms to identify those associated with an HPA response endophenotype are underway.