CNS SITES MEDIATING ALCOHOL DRINKING BEHAVIOR

调节饮酒行为的中枢神经系统站点

• 批准号: 2732453
• 负责人: JAMES M MURPHY
• 金额: $ 23.8万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2732453
• 关键词: acetylcholine; alcoholic beverage consumption; anxiety; avoidance behavior; behavior test; behavioral /social science research tag; behavioral genetics; brain electronic stimulator; dopamine; dorsal raphe nucleus; ethanol; laboratory rat; microdialysis; microinjections; neurobiology; neuropharmacology; neurotransmitter receptor; nucleus accumbens; operant conditionings; preference; reinforcer; serotonin; stereotaxic techniques; tegmentum

This proposal represents one of eight interactive R01s which are investigating hereditary influences on the biological determinants of abnormal ethanol-seeking behavior. The overall goal of the experiments in this proposal (IRG 7) is to study athe relationship between ethanol (EtOH) drinking behavior and genetically- determined differences in central nervous system (CNS) neurobiological substrates postulated to regulate the pharmacological effects of EtOH. To accomplish this goal, the experiments will require lines of rats selectively bred for divergent EtOH drinking behavior. Two sets of selected lines to be used throughout all experiments are the alcohol-preferring (P) and the -nonpreferring (NP) rats, and the hi - (HAD) and low-alcohol drinking (LAD) rats. The experiments will focus on CNS sites, and on neurotransmitter receptors and receptor subtypes at those sites, which are thought to mediate the actions EtOH. It is hypothesized that, when compared with the NP and lAD rats, rats selected for high EtOH intake (P and HAD) will exhibit innate differences at CNS sites that mediate the pharmacological consequences of EtOH. The CNS pharmacological actions of EtOH are presumed to include at least two general psychoactive effects; reinforcement and aversion. It is further hypothesized that rats innately predisposed to high EtOH intake will exhibit enhanced reinforcing effects of EtOH (euphoric and/or anxiolytic effects) and a higher threshold for the aversive consequences of EtOH ingestion. One set of experiments will examine the alterations of the reinforcing effects of EtoH drinking with CNS site-specific microdialysis of EtOH and microinjections of receptor agents. The site-specific actions of EtOH are proposed to yield behavioral consequences which reflect the pharmacological actions of EtOH at the site. Microinjections of receptor agents will provide a test of the neurotransmitter pathways involved in the reinforcing pharmacological effects of EtOH. In another set of experiments, the threshold for electrical brain stimulation reinforcement (BSR) and the effects of EtOH on BSR will be compared in rats from the selected lines. EtOH is expected to have a greater effect on BSR threshold in P and HAD than in NP and lAD rats. Sites that are found to alter EtOH drinking will subsequently be investigated with microinjections of receptor antagonists in an operant reinforcement paradigm. Sites that are found to alter EtOH drinking will also be investigated with site-specific EtOH microdialysis for CNS sites mediating aversion (conditioned taste aversion) and anxiety (plus maze). A shared resource in this IRPG (Shared Resource IV: Behavioral Testing) will provide this IRPG and others within the group (IRPGs 1,2, 3, 5 and 8) with behavioral assessment for preference for EtOH and other solutions, t ests of aversion, anxiety, reinforcement and tolerance.

该建议代表八个互动R01之一 调查遗传性影响对 异常寻求乙醇的行为。 实验的总体目标 该建议（IRG 7）是研究乙醇（ETOH）之间的关系 饮酒行为和中央遗传确定的差异 神经系统（CNS）神经生物学底物假定是为了调节 ETOH的药理作用。 为了实现这一目标，实验 将需要有选择性的大鼠排成发散的EtOH饮用 行为。 在所有实验中使用两组选定的线 是饮酒（P）和-nonprefring（NP）大鼠，以及HI - （有）和低酒精饮用（LAD）大鼠。 实验将重点放在 中枢神经系统位点，以及在这些位点上的神经递质受体和受体亚型 被认为可以介导动作EtoH的站点。 它是假设的 与NP和LAD大鼠相比，选择大鼠用于高EtOH 摄入量（P和HAT）将在中枢神经系统地点表现出天生的差异 介导ETOH的药理后果。 CNS药理 假定ETOH的动作至少包括两个一般的精神活性 效果；加强和厌恶。 进一步假设大鼠 天生对高ETOH摄入量的易感性将增强增强 ETOH（欣快和/或抗焦虑作用）和更高的阈值的影响 对于摄取EtoH的厌恶后果。 一组实验 将检查ETOH饮用的增强作用的改变 与CNS位点特异性的ETOH微透析和微注射 受体剂。 提出了ETOH的特定地点作用来产生 反映ETOH药理作用的行为后果 在现场。 受体剂的显微注射将提供测试 涉及加强药理的神经递质途径 EtoH的影响。 在另一组实验中， 脑刺激增强（BSR）和ETOH的影响 将在选定线的大鼠中比较BSR。 ETOH预计将 与NP和LAD中的BSR阈值更大 老鼠。 发现会改变eTOH饮用的网站随后将是 用手术中的受体拮抗剂显微注射调查 加固范式。 发现会改变eTOH饮酒的网站将会 也可以使用CNS位点的位点特异性ETOH微透析进行研究 介导厌恶（条件味觉厌恶）和焦虑（加上迷宫）。 此IRPG中的共享资源（共享资源IV：行为测试） 将在小组内提供此IRPG和其他人（IRPG 1,2、3、5和8） 通过对ETOH和其他解决方案偏爱的行为评估，T 厌恶，焦虑，增强和宽容的效果。