CORE--ANIMAL CORE

核心--动物核心

• 批准号: 6969885
• 负责人: KATHLEEN A GRANT
• 金额: $ 24.02万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-20 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969885
• 关键词: Macaca fascicularis; animal breeding; animal care; animal colony; behavioral /social science research tag; biomedical facility; ethanol; laboratory rat; neuropsychology; psychological reinforcement; stimulus /response

Human alcohol research and clinical practice demonstrate that, without question, individual variation in risk for excessive drinking, in sensitivity to alcohol effects, and in response to treatment strategies are critical. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse. Because macaque monkeys are so similar to human beings in their complex physiology, endocrinology, neurobiology and genetic code they can play a pivotal role in testing hypotheses generated from behavioral models that employ other species, particularly rodents. Further, the non-human primate can then be a key step in translating candidate mechanisms of ethanors effects into the human realm through the use of imaging techniques, functional genomics and behavioral outcomes. Finally, macaques can be effectively used to target mechanistic hypotheses generated by studies in humans. Thus, our primary focus of the next funding cycle for the Center for the Neurobehavioral Study of Alcohol (CNSA) is to concentrate efforts on characterizing antecedent and consequent factors related to excessive ethanol self-administration in this monkey model. To complement the non-human model of self-administration, we will also study a second animal model. Rats will be maintained under a scheduled-induced polydipsia procedure that produces excessive alcohol self-administration as evidenced by physical dependence upon withdrawal. We will use this procedure to investigate additional and complimentary mechanisms of neurobiological adaptations in response to chronic ethanol self-administration. Taken together, the CNSA will focus efforts on understanding antecedent behavioral and physiological variables as well as consequent molecular, cellular, neuroanatomical, physiological and behavioral effects of excessive self-administration of ethanol in understanding two established models of alcohol self-administration. Specific Aim 1: To provide CNSA Investigators with adult cynomolgus monkeys (Macaca fascicularis) that have undergone the following standardized ethanol self-administration procedure. Specific Aim 2: To provide CNSA Investigators with adult rats (Long Evans) that have been subjected to a standardized schedule-induced polydipsia procedure resulting in physical dependence upon ethanol.

人类酒精研究和临床实践表明，毫无疑问，过量饮酒的风险、对酒精影响的敏感性以及对治疗策略的反应的个体差异至关重要。我们的食蟹猴自我给药乙醇模型提供了一种独特且重要的酒精滥用模型。由于猕猴在复杂的生理学、内分泌学、神经生物学和遗传密码方面与人类非常相似，因此它们可以在检验其他物种（尤其是啮齿类动物）的行为模型所产生的假设方面发挥关键作用。此外，非人类灵长类动物可以成为将乙醇效应候选机制转化为人类领域的关键一步 使用成像技术、功能基因组学和行为结果。最后，猕猴可以有效地用于针对人类研究产生的机制假设。因此，我们酒精神经行为研究中心 (CNSA) 下一个资助周期的主要重点是集中精力描述与猴子模型中过量乙醇自我施用相关的前因和后果因素。为了补充非人类的自我给药模型，我们还将研究第二种动物模型。将大鼠维持在预定诱导的多饮程序下，该程序产生过量的酒精自我施用，如戒断后的身体依赖性所证明的。我们将使用此程序来研究神经生物学的附加和补充机制 对长期乙醇自我给药的适应。总而言之，CNSA 将集中精力了解先前的行为和生理变量，以及过度自我服用乙醇对后续分子、细胞、神经解剖学、生理和行为的影响，以了解两种既定的自我服用酒精模型。 具体目标 1：为 CNSA 研究人员提供经过以下标准化乙醇自我给药程序的成年食蟹猴（Macaca fascicularis）。 具体目标 2：为 CNSA 调查人员提供成年大鼠（Long Evans），这些大鼠已接受标准化时间表诱导的烦渴程序，导致对乙醇的身体依赖。