PHARMACOGENETIC ANALYSIS OF LOW-DOSE ETHANOL EFFECTS

低剂量乙醇作用的药理学分析

• 批准号: 3112525
• 负责人: BYRON C JONES
• 金额: $ 9.09万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3112525
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavior disorders; behavior test; chordate locomotion; dopamine receptor; dosage; drug adverse effect; ethology; exploratory behavior; frontal lobe /cortex; genetic polymorphism; genetic strain; high performance liquid chromatography; hypothalamus; laboratory mouse; neurochemistry; neurotensin; neurotransmitter metabolism; nucleus accumbens; pharmacogenetics; putamen; radioimmunoassay; reinforcer; tegmentum

The research outlined in this proposal examines genetic influences on behavioral responses to low doses of ethanol and neurochemical events which underlie low-dose ethanol sensitivity. Recombinant inbred strains and selected lines of mice which evince widely differential behavioral responses to low doses of ethanol will be used to generate genetic correlational analyses among behaviors and between behavioral and neurochemical measures. The behaviors of interest include locomotor activity, exploration and indices of anxiety, i.e., thigmotaxis and plus- maze performance. Specific neurochemical mechanisms of interest in low- dose ethanol behavioral response include dopamine metabolism and neurotensin levels in discrete areas of the fore and midbrain. Specific structures include the nucleus accumbens, ventral tegmentum, caudate- putamen and frontal cortex. Specific dopamine receptor agonists and antagonists [both D1 and D2] will be applied centrally, concomitantly with i.p. administration of doses of ethanol which maximally differentiate strain/line-related behavioral response to low doses of ethanol. The long- term goal of this research is to define genetically based neurochemical mechanisms mediating effects of low doses of ethanol. Ultimately these studies will have general heuristic value in understanding alcohol-seeking behavior and alcoholism.

本提案中概述的研究考察了遗传对 对低剂量乙醇的行为反应和神经化学事件 低剂量乙醇敏感性的基础。 重组近交系和 表现出广泛差异行为的小鼠的选定品系 对低剂量乙醇的反应将被用来产生遗传 行为之间以及行为与行为之间的相关性分析 神经化学措施。 感兴趣的行为包括运动 活动、探索和焦虑指数，即趋触性和加- 迷宫表演。 低水平感兴趣的特定神经化学机制 剂量乙醇行为反应包括多巴胺代谢和 前脑和中脑离散区域的神经降压素水平。 具体的 结构包括伏隔核、腹侧被盖、尾状核 壳核和额叶皮质。 特异性多巴胺受体激动剂和 拮抗剂 [D1 和 D2] 将集中应用，同时 ip施用最大程度区分的乙醇剂量 对低剂量乙醇的菌株/品系相关行为反应。 长- 这项研究的长期目标是定义基于遗传的神经化学物质 介导低剂量乙醇作用的机制。 最终这些 研究对于理解饮酒行为具有普遍的启发价值 行为和酗酒。