CNS sites for the Rewarding Actions of Alcohol

CNS 酒精奖励行为网站

基本信息

批准号：
9020182
负责人：
WILLIAM J MCBRIDE
金额：
$ 34.65万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2018-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The long-range goals of this project are to elucidate mechanisms involved in the CNS rewarding actions of ethanol, and the contribution of these rewarding effects toward maintaining high alcohol drinking. The overall hypothesis to be tested is that responsiveness of the limbic system to the reinforcing, stimulating effects of ethanol (EtOH) contributes toward the initiation of alcohol drinking and development of high alcohol drinking. The intra-cranial self-administration (ICSA) technique will be used to examine the reinforcing effects of EtOH and certain receptor agents within discrete regions. The micro-injection/micro-dialysis procedure will be use to assess the response of the meso-limbic dopamine (DA) system to the stimulating actions of EtOH and selected receptor agents. Aim 1 will test the hypothesis that the reinforcing effects of EtOH within the nucleus accumbens (ACB) shell are mediated by serotonin-3 (5-HT3), and/or 5-HT2A receptors. Aim will determine the involvement of the caudal ventral pallidum (VP) and/or the dorsal medial prefrontal cortex (mPFC) in mediating the reinforcing actions of EtOH. Aim 3 will examine neuronal mechanisms within the posterior ventral tegmental area (pVTA) that underlie the increased sensitivity and responsiveness of this region to the reinforcing effects of EtOH following chronic alcohol drinking. Aim 4 will test the hypothesis that alterations in the 5-HT3 receptor and D2 auto-receptor contribute to the development of sensitization to the stimulating effects of EtOH within the pVTA. To assess possible genetic influences on the rewarding, stimulating effects of EtOH within the limbic system, selected experiments will be conducted with alcohol-preferring (P) rats and stock Wistar rats. The results of this project will provide important information on (a) CNS sites and receptors mediating the reinforcing effects of EtOH, (b) neuronal mechanisms underlying the increased responsiveness of the pVTA to the stimulating, reinforcing effects of EtOH produced by chronic or repeated EtOH exposure, and (c) genetic influences on the reinforcing responses to EtOH. A better understanding of the complex basic brain mechanisms that contribute to high alcohol drinking behavior is critical for the development of treatment strategies for alcohol abuse.

描述（由申请人提供）：该项目的长期目标是阐明乙醇的中枢神经系统奖励作用的机制，以及这些奖励作用对维持高酒精饮酒的贡献。要测试的总体假设是，边缘系统对乙醇 (EtOH) 的强化、刺激作用的反应有助于饮酒的开始和高度饮酒的发展。颅内自我给药（ICSA）技术将用于检查乙醇和某些受体药物在离散区域内的增强作用。微注射/微透析程序将用于评估中脑边缘多巴胺 (DA) 系统对 EtOH 和选定受体药物的刺激作用的反应。目标 1 将检验伏隔核 (ACB) 壳内 EtOH 的增强作用是由 5-羟色胺-3 (5-HT3) 和/或 5-HT2A 受体介导的假设。目的将确定尾部腹侧苍白球 (VP) 和/或背侧内侧前额叶皮层 (mPFC) 在介导 EtOH 增强作用中的参与。目标 3 将检查后腹侧被盖区 (pVTA) 内的神经元机制，该机制是该区域对长期饮酒后乙醇增强作用的敏感性和反应性增加的基础。目标 4 将检验以下假设：5-HT3 受体和 D2 自身受体的改变有助于 pVTA 内 EtOH 刺激作用的敏感性发展。为了评估边缘系统内乙醇对奖励和刺激作用的可能遗传影响，将在嗜酒 (P) 大鼠和 Wistar 大鼠中进行选定的实验。该项目的结果将提供以下方面的重要信息：(a) 介导 EtOH 增强作用的 CNS 位点和受体，(b) pVTA 对慢性或反复 EtOH 产生的 EtOH 刺激、增强作用的反应性增加的神经元机制暴露，以及（c）遗传对乙醇增强反应的影响。更好地了解导致大量饮酒行为的复杂基本大脑机制对于制定酒精滥用治疗策略至关重要。