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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。GCRC的神经系统实验室提出了一项关于人类酒精剥夺效应（ADE）的试点研究。几乎未在人体中进行过研究，在动物研究中将ADE定义为在强制禁欲一段时间后显著增加但短暂的乙醇自愿摄入，以达到固定效果。大鼠研究产生了一个强大的ADE，与其遗传遗产有很强的关联，但这些方法不能在人类中伦理地使用。或者，大脑对酒精反应的遗传指数可以在人类中精确测量，如果两次测试中暴露于酒精的时间过程相同，这些指数的变化可能归因于测试期间的禁欲。初步研究的目的是证明量化人体ADE的可行性，并评估正式研究中提出的一系列依赖性指标的效应量。先导研究设计测试大脑对酒精的反应，使用与赞助研究（酒精中毒风险的新表型遗传性）相同的程序。另一方面，它关注的是一个小得多的样本人群，比父母的研究喝得更多，并采用个别受试者，而不是兄弟姐妹对。两组非依赖性的、健康的、非成年的、重度饮酒者将跟踪他们通常的饮酒习惯5天，然后在60mg%下进行BrAC钳夹，同时测量大脑的反应。然后，一组将开始5天的监测戒酒，而另一组继续他们的正常饮酒习惯;然后重复测试大脑功能。将个体大脑对酒精反应的变化定义为ADE;将使用组统计量评估ADE的效应量。

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.