A PILOT STUDY ASSESSING THE ALCOHOL DEPRIVATION EFFECT IN HUMANS AS A POTENTI

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。GCRC的神经系统实验室提议对人类的酒精剥夺效应(ADE)进行一项初步研究。在人类中几乎没有研究过的ADE在动物研究中被定义为在强制禁欲一段时间后大幅增加但短暂的自愿乙醇摄入量，以达到固定的效果。老鼠研究产生了一种强大的ADE，与它们的遗传遗传有很强的关联，但这种方法不能在人类身上进行伦理上的应用。或者，大脑对酒精反应的可遗传指数可以在人类中精确测量，如果两个测试阶段接触酒精的时间过程相同，这些指数的变化可能归因于两个测试阶段之间的禁欲。这项初步研究的目标是论证量化人类ADE的可行性，并评估正式研究中提出的一系列依赖措施的影响大小。先导研究设计使用与赞助研究(酒精中毒风险的新表型的遗传性)相同的程序来测试大脑对酒精的反应。另一方面，它关注的样本人群要小得多，他们比父母的研究喝得更多，而且使用单独的受试者，而不是兄弟姐妹对。两组不依赖的、健康的、年轻的、大量饮酒的人将被跟踪他们通常的饮酒习惯5天，然后接受60 mg%的胸夹，同时测量大脑的反应。然后，一组人将开始为期5天的戒酒监测，而另一组人将继续保持正常的饮酒习惯；然后重复进行大脑功能测试。个体大脑对酒精反应的变化将被定义为ADE；群体统计将用于评估ADE的影响大小。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The GCRC's Neural Systems Laboratory proposes a pilot study of the alcohol deprivation effect (ADE) in humans. Virtually unstudied in people, the ADE is defined in animal studies a substantially increased, but transient voluntary intake of ethanol after an interval of imposed abstinence in order to achieve a fixed effect. Rat studies produce a robust ADE, with strong associations to their genetic heritage, but the methods cannot be employed ethically in humans. Alternatively, heritable indices of the brain's response to alcohol can be measured precisely in humans, and changes in those indices might be attributable to abstinence between testing sessions, if the time course of exposure to alcohol is identical in both testing sessions. The goal of the pilot study is to demonstrate feasibility of quantifying the ADE in humans and to assess the effect sizes for the battery of dependent measures that would be proposed in formal studies. The pilot study design tests the brain's response to alcohol using the same procedures that the sponsoring study (Heritability of novel Phenotypes of the Risk for Alcoholism) employed. On the other hand, it focuses on a much smaller sample population that drinks more heavily than the parent study, and employs individual subjects rather than sibling pairs. Two groups of non-dependent, healthy, young-adult, heavy drinkers will have their usual drinking habits tracked for 5 days, then undergo a BrAC clamp at 60mg% while the brain's response is measured. Then one group will commence 5 days of monitored abstinence from alcohol while the other continues their regular drinking habits; followed by a repetition of the testing of brain function. Changes in individual brain response to alcohol will be defined as the ADE; group statistics will be used to assess the effect size of the ADE.