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，过度饮酒的风险，对酒精效应的敏感性以及对治疗策略的响应至关重要。我们在Cynomolgus Monkeys中乙醇自我给药的模型提供了一种独特而重要的酗酒模型。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中与人类非常相似，因此可以在测试由采用其他物种（尤其是啮齿动物）的行为模型产生的假设中发挥关键作用。此外，非人类灵长类 成像技术，功能基因组学和行为结果的使用。最后，猕猴可有效地用于针对人类研究产生的机械假设。因此，我们对酒精神经行为研究中心的下一个融资周期（CNSA）的主要重点是将努力集中在该猴子模型中与过度乙醇自我给药相关的先例和随之而来的因素。为了补充非人类的自我管理模型，我们还将研究第二种动物模型。大鼠将在预定的诱导的多次手术中维持，该程序会产生过量的酒精自我给药，这可以通过对戒断的身体依赖来证明。我们将使用此程序来研究神经生物学的其他和免费的机制 响应慢性乙醇自我给药的适应。综上所述，CNSA将集中精力理解先决的行为和生理变量，以及随之而来的分子，细胞，神经解剖学，生理和行为影响乙醇过多地自我给予乙醇在理解两个既定的酒精自身给药模型中的自我影响。 具体目的1：为CNSA研究人员提供成人cynomolgus猴子（Macaca fascicularis），这些猴子接受了以下标准化的乙醇自我给药程序。 具体目的2：为CNSA研究人员提供成年大鼠（长埃文斯），这些大鼠已受到标准化的进度诱导的多二虫手术，从而导致物理依赖乙醇。