ALCOHOL PREDISPOSITION: COMPARATIVE WITHDRAWAL SYNDROMES

酒精易感性：比较戒断综合症

• 批准号: 3109448
• 负责人: JOHN K BELKNAP
• 金额: $ 9.84万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109448
• 关键词: GABA receptor; alcoholism /alcohol abuse; autoradiography; benzodiazepine receptor; butanols; convulsants; convulsions; diazepam; disease /disorder proneness /risk; drug addiction; drug withdrawal; ethanol; gene frequency; genetic disorder; genetic strain; laboratory mouse; model design /development; morphine; nitrous oxide; phenobarbital; pleiotropism

It is proposed to conduct investigations to utilize and further characterize newly developed genetic lines of mice which have been selectively-bred for either increased or decreased handling- induced convulsions (HIC) following withdrawal from ethanol (WSP and WSR lines). It is planned to determine if these genetically- based differences in susceptibility to HIC associated with physical dependence on ethanol are genetically related to susceptibility (cross-susceptibility) to HIC and other withdrawal signs associated with physical dependence on benzodiazepines, barbiturates, acetaldehyde, anesthetic gases, t-butanol, and several other sedative-hypnotic drugs. If so, then this would suggest that the mechanisms responsible for the intensity of HIC following ethanol withdrawal are also operative with these other drugs and/or withdrawal signs. Conversely, if ethanol HIC susceptibility does not generalize to these other drugs and/or withdrawal signs monitored, then independent controlling mechanisms are implicated. The development of these selected lines allows a novel approach to be utilized to determine the degree of commonality that exists among a number of drug dependencies with respect to alcohol. Additional studies are proposed to assess the role of the GABA and benzodiazepine receptors in the genesis of the alcohol withdrawal syndrome, utilizing in vitro receptor binding and receptor autoradiography in the WSP, WSR mice. The latter technique in particular will allow the detection of very small changes in receptor density caused by chronic intoxication and subsequent withdrawal from ethanol.

建议开展调查以利用并进一步 描述了新开发的小鼠遗传系的特征 经过选择性培育以增加或减少处理- 戒断乙醇后诱发惊厥 (HIC) (WSP 和 WSR 线）。 计划确定这些基因是否- 与体质有关的 HIC 易感性差异 对乙醇的依赖与遗传易感性有关 （交叉易感性）对 HIC 和其他相关戒断症状 对苯二氮卓类药物、巴比妥类药物有身体依赖性， 乙醛、麻醉气体、叔丁醇和其他几种 镇静催眠药。 如果是这样，那么这表明 乙醇后 HIC 强度的机制 戒断也可与这些其他药物一起使用和/或 撤药迹象。 相反，如果乙醇 HIC 敏感性不 不能推广到这些其他药物和/或戒断症状 监控，然后独立的控制机制 受牵连。 这些选定产品线的开发允许 用于确定程度的新颖方法 许多药物依赖之间存在共性 关于酒精。 建议进行更多研究来评估 GABA 的作用 和苯二氮卓受体在酒精的起源中 戒断综合症，利用体外受体结合和 WSP、WSR 小鼠的受体放射自显影。 后者 特别是技术将允许检测非常小的 慢性中毒引起的受体密度变化 随后从乙醇中退出。