Stress, Rearing, and Ethanol Reinforcement in Monkeys

猴子的压力、饲养和乙醇强化

• 批准号: 6943142
• 负责人: james H Woods
• 金额: $ 30.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943142
• 关键词: Macaca mulatta; alcoholism /alcohol abuse; behavioral /social science research tag; benzodiazepine receptor; biological models; early experience; ethanol; hypothalamic pituitary adrenal axis; intravenous administration; motivation; neuropharmacology; neurotransmitter agonist; piperazines; psychological stressor; reinforcer; self medication; stress; yohimbine

DESCRIPTION (provided by applicant): Alcoholism is a major public health problem in the United States, resulting in the annual death of tens of thousands of Americans and costing billions of dollars. The development of animal models of alcoholism will play an important role in understanding the biological factors that contribute to the development of alcoholism and provide a means of testing novel medications for its treatment. A nonhuman primate model of alcoholism has been developed at the NIAAA's Laboratory of Clinical Studies in which animals are subjected to one of three different rearing manipulations that are designed to expose them to varying degrees of early life stress. When tested years later, significant group differences in oral ethanol self-administration behavior are observed. The first aim of the current application is to generate a detailed neuroendocrinological profile for eight monkeys in each of the three rearing groups (n=24) by measuring the dose-effect and time-course of the HPA axis response to the alpha 2 adrenergic antagonist yohimbine, the mixed serotonin agonist mCPP, the benzodiazepine receptor inverse agonist beta-carboline-3-carboxylic acid ethyl ester, and the putative CRHR1 receptor agonist EG1. The second aim is to quantify individual and group differences among the animals in their motivation to intravenously self-administer ethanol by examining the extent to which they persist on a progressive ratio schedule of intravenous ethanol reinforcement. The third aim is to determine whether there are individual and/or group differences in the effect that the pharmacological stressors administered in Experiment 1 have on progressive ratio performance for intravenous ethanol self-administration when given as pretreatments. These studies will contribute to a better understanding of the biological basis of alcoholism, which is a first step toward the development of effective pharmacotherapeutic interventions.

描述（由申请人提供）：酗酒是美国的一个主要公共卫生问题，每年导致数万名美国人死亡，造成数十亿美元的损失。酒精中毒动物模型的开发将在了解导致酒精中毒发展的生物学因素方面发挥重要作用，并提供测试治疗酒精中毒的新药物的手段。 NIAAA 临床研究实验室开发了一种非人类灵长类酒精中毒模型，其中动物接受三种不同的饲养操作之一，旨在使它们承受不同程度的早期生活压力。几年后进行测试时，观察到口服乙醇自我给药行为存在显着的群体差异。当前应用的第一个目标是通过测量 HPA 轴对 α2 肾上腺素能拮抗剂的反应的剂量效应和时程，为三个饲养组（n = 24）中每组的八只猴子生成详细的神经内分泌学概况育亨宾、混合血清素激动剂 mCPP、苯二氮卓受体反向激动剂 β-咔啉-3-羧酸乙酯和假定的 CRHR1受体激动剂EG1。第二个目标是通过检查动物坚持静脉内乙醇强化的渐进比例计划的程度，量化动物静脉内自我施用乙醇的动机之间的个体和群体差异。第三个目的是确定实验1中施用的药理应激源对作为预处理给予的静脉内乙醇自我施用的渐进比率表现的影响是否存在个体和/或组差异。这些研究将有助于更好地了解酗酒的生物学基础，这是开发有效药物治疗干预措施的第一步。