ALCOHOL, NICOTINIC RECEPTORS AND MESOLIMBIC SYSTEM

酒精、烟碱受体和中脑边缘系统

• 批准号: 6200929
• 负责人: YOUSEF TIZABI
• 金额: $ 16.86万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6200929
• 关键词: brain metabolism; dopamine; dosage; ethanol; high performance liquid chromatography; laboratory rat; limbic system; mecamylamine; microinjections; nicotinic receptors; preference; psychopharmacology; reinforcer; tegmentum

Alcoholism is a major public health problem in the United States and many parts of the world. There exists a strong positive association between alcohol consumption and cigarette smoking (nicotine intake). In contrast to nicotine, however, no specific receptor for ethanol has been found. The mesolimbic dopaminergic pathway projecting from the ventral tegmenta area (VTA) to the nucleus accombens (NACC) is believed to be intimately involved in the reinforcing properties of the addictive drugs including alcohol and nicotine. Nicotinic receptors are present in both VTA and NACC. There is strong suggestion that the stimulatory action of ethanol on the mesolimbic system might also be mediated by nicotinic receptors located in this pathway. This proposal will test the hypotheses that 1) activation of nicotinic receptors promotes the actions of ethanol in a brain reward pathway, and 2) alcohol preferring P rats have an altered nicotinic receptor-mediated response to ethanol when compared with stock Wistar and alcohol- nonpreferring NP rats. Micro dialysis and HPLC-EC procedures will be used to determine the dose-response effects of micro injecting nicotinic agonists (nicotine and cytisine) or antagonist (mecamylamine) into the VTA and measuring extracellular levels of DA in the shell portion of the NACC of Wistar rats. Moreover, the effects of a sub- maximal dose of nicotine microinjected into the VTA, on ethanol- induced DA release inthe NACC shell of the Wistar, P, and NP rats will be evaluated. This pilot project will provide essental preliminary data to pursue more extensive studies to examine the involvement of nicotinic receptors in alcoholism and alcohol abuse. This line of research has the potential of leading to novel pharmacotherapies for simultaneous interventions in alcoholism and smoking cessation.

酗酒是美国的一个主要公共卫生问题 世界许多地方。 存在很强的正相关性 饮酒和吸烟（尼古丁摄入量）之间的关系。 然而，与尼古丁相反，乙醇没有特定的受体 被发现了。 中脑边缘多巴胺能通路从 腹侧被盖区 (VTA) 到伴核 (NACC) 的位置是 据信与增强性能密切相关 成瘾药物包括酒精和尼古丁。 烟碱受体是 存在于 VTA 和 NACC 中。 有强烈建议称 乙醇对中脑边缘系统的刺激作用也可能是 由位于该途径的烟碱受体介导。 这个提议 将测试以下假设：1) 烟碱受体的激活 促进乙醇在大脑奖励通路中的作用，2) 偏好酒精的 P 大鼠具有改变的烟碱受体介导的 与库存 Wistar 和酒精相比，对乙醇的反应 非偏好 NP 大鼠。 微透析和 HPLC-EC 程序将 用于确定微量注射的剂量反应效应 烟碱激动剂（尼古丁和金雀花碱）或拮抗剂（美加明） 进入 VTA 并测量壳中 DA 的细胞外水平 Wistar 大鼠 NACC 的一部分。 此外，子的影响 将最大剂量的尼古丁显微注射到 VTA 中，用乙醇- 诱导 Wistar、P 和 NP 大鼠 NACC 壳中 DA 的释放 将被评估。 该试点项目将提供必要的初步 数据进行更广泛的研究，以检验 酒精中毒和酒精滥用中的烟碱受体。 这条线的 研究有可能带来新的药物疗法 同时干预酗酒和戒烟。