ETHANOL DISCRIMINATION AND G PROTEIN COUPLING IN BRAIN

大脑中的乙醇歧视和 G 蛋白偶联

• 批准号: 6563226
• 负责人: DANA E SELLEY
• 金额: $ 17.85万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563226
• 关键词: G protein; autoradiography; behavioral /social science research tag; brain; ethanol; hippocampus; laboratory rat; neuroanatomy; neuropsychology; opioid receptor; protein structure function; psychopharmacology; psychophysics; receptor binding; receptor coupling; serotonin; serotonin receptor; stimulus /response; substance abuse related behavior

The discriminative stimulus properties of alcohol may contribute to its abuse and addiction potential in humans. Animal models of alcohol discrimination have indicated the involvement of serotonin (5-HT) receptors, including the G/i/o-coupled 5-HT/lB/D receptors, in mediating the discriminative stimulus properties of alcohol. The main hypothesis of the proposed pilot study is that the acquisition of ethanol discrimination in rats is associated with changes in 5-HT/l receptor activity. A technique has been developed in our laboratory, whereby receptor-coupled G-protein activity is measured by agonist-stimulated [35S]GTPgammaS autoradiography in tissue sections. This technique allows quantification of the biochemical activity of G-protein-coupled receptors with a high degree of anatomical resolution. This methodology is ideally suited to the study of the effects of the acquisition of ethanol discrimination on 5-HT1 receptor-coupled G-protein activity. Regions where changes in 5-HT1 receptor-coupled G-protein activity are observed autoradiographically will be dissected, and more quantitative biochemical and pharmacological analysis will be performed using both agonist-stimulated [35S]GTPgammaS binding and receptor binding in membranes. This approach, which combines behavioral pharmacology with neuroanatomy and signal transduction biochemistry, may elucidate the neuroadaptive role of 5-HTl receptors in the development of ethanol discrimination. This pilot project directly addresses the Center aims regarding the possible cellular mechanisms underlying ethanol's discriminative stimulus effects. It will provide import pilot data that can supplement the studies performed in Project 3 of the Center, as well as provide information for the R01 work conducted by Dr. Grant.

酒精的歧视性刺激特性可能有助于其在人类中的滥用和成瘾潜力。酒精歧视的动物模型表明5-羟色胺（5-HT）受体，包括G/I/O偶联的5-HT/LB/D受体，参与介导酒精的歧视性刺激特性。拟议的试点研究的主要假设是，大鼠中乙醇歧视的获取与5-HT/L受体活性的变化有关。我们的实验室已经开发了一种技术，从而通过激动剂刺激的[35S] GTPGAMMAS放下自显影在组织切片中测量受体偶联的G蛋白活性。该技术允许定量具有高度解剖学分辨率的G蛋白偶联受体的生化活性。该方法理想地适合研究乙醇歧视对5-HT1受体偶联G蛋白活性的影响。将在自显影下观察到5-HT1受体偶联的G蛋白活性的变化，并使用激动剂刺激的[35S] GTPGAMMAS gtpgammas和受体结合在膜中进行更定量的生化和药理学分析。这种方法将行为药理学与神经解剖学和信号转导生物化学相结合，可以阐明5-HTL受体在乙醇识别发展中的神经适应性作用。该试点项目直接解决了该中心的目的，涉及乙醇歧视性刺激效应的可能的细胞机制。它将提供可以补充中心项目3中研究的进口试点数据，并为Grant博士进行的R01工作提供信息。