Alcohol Binging: Disruptions in Impulse Control and 5-HT as Underlying Mechanisms

描述(申请人提供)：这项研究的目的是确定狂饮的成年人如何受到模拟的酒精狂欢和5-羟色胺合成减少的不同影响。与适度社交饮酒不同，狂欢饮酒指的是由禁酒期隔开的几次重度饮酒。许多大学生酗酒，这一直是大多数研究的重点。但是，大多数酗酒者并不是大学生，那些在大学毕业后继续酗酒的人是一个被忽视的群体。对于理解酗酒可能很重要的一个机制是对酒精摄入量的“失控”，这被认为是区分酗酒个人和适度社交饮酒的一个基本过程。酒精对狂欢行为的影响可能部分与5-羟色胺能失调和行为冲动的潜在机制有关。但是，酒精消费和5-羟色胺失调对大学以上酗酒者行为冲动的影响还没有得到测试。在这里，年龄在24岁到34岁之间的酗酒者(n=48)和不酗酒者(n=48)将从社区中招募，并在清醒时和在5-羟色胺合成减少后模拟饮酒期间进行研究，以确定这些条件如何影响实验室测量的冲动。三种独特的冲动测量将被用来评估在模拟酗酒(或安慰剂)过程之前、期间和之后的多个时间点的群体差异。4个主要实验条件包括L-色氨酸耗竭(5-羟色胺合成减少)和L-色氨酸平衡对照(维持5-羟色胺合成)后给予酒精或安慰剂。这项研究的目的是确定：(1)模拟酗酒是否比适度饮酒更能增加酗酒者的冲动；(2)5-羟色胺合成的减少在多大程度上影响酗酒和适度饮酒者的冲动，以及这些减少如何影响模拟狂欢期间酒精诱导的冲动。第二个目的是确定在最初的“启动”酒精剂量后，观察到的冲动变化与随后的饮酒选择之间的关系。这个次要目标包括评估在饮酒前和饮酒后冲动测量指标的群体差异，然后进行一次临时饮酒。这些目的是为了研究酒精和个人潜在的生物状态(即5-羟色胺合成减少)是如何影响“失控”(即冲动)的，后者被认为是导致狂欢发作的原因。这项研究的创新和临床意义在于，它以新的方式结合了方法来检查研究不足的人群，并解决了文献中存在的动物模型和狂饮流行病学特征之间的差距。在这样做的过程中，我们将澄清假设为有助于维持狂欢插曲的机制的作用。 公共卫生相关性：这项研究解决了在理解酒精和潜在生物状态的个体差异如何影响与酗酒有关的行为过程方面的关键差距。这项研究将提供数据，以澄清冲动行为和5-羟色胺功能作为维持酗酒事件的机制所起的作用。有了这种理解，我们就可以利用认知-行为和药物策略来开发旨在破坏这种机制的治疗方法。

DESCRIPTION (provided by applicant): The purpose of this study is to determine how adults who binge drink are differentially affected by a simulated alcohol binge and reduction of serotonin synthesis. Unlike moderate social drinking, binge drinking involves engaging in episodes of heavy drinking separated by periods of abstinence. Many college students engage in binge drinking, which has been the focus of the majority of research. But, most binge drinkers are not college students and those who continue binging behavior beyond the college years are an understudied group. One mechanism that may be important to understanding alcohol binging is a "loss of control" of alcohol intake, which is hypothesized to be a fundamental process that distinguishes individuals who engage in binge drinking from those who engage in moderate social drinking. Alcohol's effects on binging behaviors may be related, in part, to underlying mechanisms of serotonergic dysregulation and behavioral impulsivity. But, the effects of alcohol consumption and serotonin dysregulation on behavioral impulsivity among binge drinkers beyond college age have not been tested. Here, Binge (n = 48) and Non-Binge (n = 48) drinkers, ages 24 to 34, will be recruited from the community and studied while sober and during a simulated alcohol binge after reductions in serotonin synthesis to determine how these conditions affect laboratory-measured impulsivity. Three unique measures of impulsivity will be used to assess group differences at multiple time points before, during, and after a simulated alcohol (or placebo) binge procedure. The 4 primary experimental conditions include alcohol or placebo administered after L-tryptophan Depletion (reduced serotonin synthesis) and after L- tryptophan Balanced Control (maintained serotonin synthesis). The aims of this study are to determine: (1) whether a simulated alcohol binge increases impulsivity in binge drinkers more than moderate drinkers; and (2) to what extent reductions in serotonin synthesis affect impulsivity in both binge and moderate drinkers, and how these reductions affect alcohol-induced impulsivity during a simulated binge. A secondary aim is to determine how changes observed in impulsivity after an initial "priming" dose of alcohol relate to subsequent choices for consuming additional alcohol. This secondary aim includes assessment of group differences in measures of impulsivity prior to and after a "priming" dose of alcohol, followed by a session of ad libitum alcohol consumption. These aims are designed to examine how "loss of control" (i.e., impulsivity) is affected by alcohol and by an individual's underlying biological state (i.e., reduced serotonin synthesis), which have been proposed as contributing to binging episodes. The innovation and clinical significance of this study is that it combines methodologies in novel ways to examine an understudied population and address gaps in the literature that exist between animal models and epidemiological characterizations of binge drinking. In doing so, we will clarify the role of mechanisms hypothesized as contributing to the maintenance of a binge episode. PUBLIC HEALTH RELEVANCE: This study addresses critical gaps in understanding how alcohol and individual differences in underlying biological states affect behavioral processes involved in binge alcohol drinking. This study will yield data to clarify the role of impulsive behavior and serotonin function as mechanisms that contribute to the maintenance of an alcohol binge-drinking episode. With this understanding, we can develop treatments aimed at disrupting such mechanisms using cognitive-behavioral and pharmacological strategies.