STRESS AND ETHANOL SELF-ADMINISTRATION IN MONKEYS

猴子的压力和乙醇自我管理

• 批准号: 8357781
• 负责人: KATHLEEN A GRANT
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357781
• 关键词: Address; Adrenal Glands; Alcohol abuse; Alcohol consumption; Behavior; Chronic; Corticotropin; Endocrine; Ethanol; Funding; Genes; Genetic Polymorphism; Grant; Hormones; Hydrocortisone; Hypothalamic structure; Individual; Individual Differences; Measurable; Monkeys; National Center for Research Resources; Nature; Output; Phenotype; Pituitary Gland; Population; Population Distributions; Primates; Principal Investigator; Procedures; Research; Research Infrastructure; Resources; Risk; Role; Self Administration; Self-Administered; Source; Stress; Stressful Event; United States National Institutes of Health; cost; endophenotype; hypothalamic-pituitary-adrenal axis; response

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 压力被认为是滥用乙醇的病因学因素。但是，压力在过度乙醇消耗的风险中的作用很难从过量饮酒所带来的压力中解脱出来。一个起点是，通过从垂体中垂体和皮质醇的肾上腺皮质激素（ACTH）的循环水平的可测量变化来定义应力，因为下丘脑 - 垂体 - 肾上腺（HPA）轴的激活。猴子在HPA轴对压力事件的内分泌反应中表现出明显的个体差异，并且在他们选择自我管理的乙醇量上也清除了个体差异。为了解决压力和过度乙醇相互作用的因果相互作用，我们提议在慢性乙醇自我给药之前，之中和之后表征HPA对压力反应的个体差异。此外，内分泌对压力的反应的本质使焦点是信息流，集成和功能输出的神经记录的概念。将HPA响应视为行为的中间决定因素，将转化努力转化为中间表型或“末日型”的领域。为了解决HPA响应作为过度乙醇自我给药风险的基础的HPA响应的预测有效性，我们已经筛选了大量的猴子以用于特定的HPA反应。在乙醇自我管理程序中，表征了潜在内表型的人口分布极端的个体。基因多态性以鉴定与HPA反应内表型相关的基因多态性正在进行中。