BENZODIAZEPINE SENSITIVITY IN SONS OF ALCOHOLICS

酗酒者儿子对苯二氮卓类药物的敏感性

• 批准号: 3452826
• 负责人: DEBORAH S COWLEY
• 金额: $ 11.62万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3452826
• 关键词: GABA receptor; adolescence (12-20); alcoholism /alcohol abuse; alcoholism /alcohol abuse prevention; behavioral genetics; benzodiazepine receptor; biomarker; blood chemistry; diazepam; disease /disorder proneness /risk; drug adverse effect; drug tolerance; eye movement disorders; human subject; interview; longitudinal human study; male; memory; neurochemistry; neuropsychological tests; parent offspring interaction; paternal behavior; receptor sensitivity; urinalysis; young adult human (21-34)

The aim of this study is to determine whether increased risk for alcoholism is associated with differences in the functional sensitivity of the GABA A- benzodiazepine receptor system. Alcoholism is in part genetically determined. Sons of alcoholic fathers, who are at particularly high risk for alcoholism, appear less sensitive to the effects of ethanol than are control subjects. Since ethanol affects membrane fluidity and numerous neurotransmitter system , the reason for this apparent subsensitivity remains to be determined. Ethanol increases chloride conductance at the GABA A-benzodiazepine receptor, thus potentiating GABAergic neurotransmission. Animal studies have implicated effects of ethanol on the GABA A-benzodiazepine receptor system in ethanol intoxication, tolerance, and dependence. However, the role of this receptor system in vulnerability to alcoholism has not yet been examined. Since the GABA A receptor is the primary site of action of benzodiazepines, this study will use the effects of acute administration of diazepam as a specific measure of receptor function. Diazepam effects will be assessed in sons of alcoholics and control subjects using reduction in saccadic eye movement velocity (SEMV), a reliable, quantitative, dose-dependent index of GABA A-benzodiazepine receptor function, as well as self-rated sedation and intoxication, memory, epinephrine, and norepinephrine. Findings of differences in benzodiazepine sensitivity in sons of alcoholics versus controls may provide a possible neurochemical basis for subsensitivity to ethanol in son of alcoholics and a potential biologic marker linked with the actions of ethanol at the receptor level. Differences between sons of type 1 versus type 2 alcoholics and those with multiple versus a single (i.e. their father) alcoholic relative will also be assessed.

这项研究的目的是确定是否增加了酒精中毒的风险 与GABA A-功能敏感性的差异有关 苯二氮卓受体系统。 酒精中毒部分是遗传确定的。酗酒父亲的儿子， 谁在酒精中毒的风险特别高，似乎对 乙醇的影响比对照组受试者。由于乙醇会影响 膜流动性和众多神经递质系统，原因 这种明显的下敏性尚待确定。乙醇增加 GABA A-苯二氮卓受体处的氯化物电导，因此 增强GABA能神经传递。动物研究牵涉 乙醇对乙醇中GABA A-苯二氮卓受体系统的影响 中毒，耐受性和依赖性。但是，该受体的作用 尚未检查易受酒精中毒的系统。 由于GABA A受体是苯二氮卓类药物的主要作用部位，因此 这项研究将使用地西epa急性给药作为一个 受体功能的特定度量。地西epa效应将在 酗酒者和控制受试者的儿子使用saccadic Eye的降低 运动速度（SEMV），一个可靠的，定量的，剂量依赖的指数 GABA A-苯二氮卓受体功能以及自评镇静和 中毒，记忆，肾上腺素和去甲肾上腺素。 酗酒儿子苯二氮卓敏感性差异的发现 对照对照可能会提供可能的神经化学基础 酗酒者和潜在生物学的对乙醇的敏感性 标记与乙醇在受体水平上的作用有关。 1型儿子与2型酗酒者之间的差异 多个与单个（即他们的父亲）的酗酒亲戚也将 被评估。