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

描述（由申请人提供）：本研究的目的是确定酗酒的成年人如何受到模拟酒精狂欢和血清素合成减少的不同影响。与适度的社交饮酒不同，狂饮涉及到大量饮酒的发作，其间间隔着戒酒期。许多大学生酗酒，这一直是大多数研究的焦点。但是，大多数酗酒者不是大学生，那些在大学毕业后继续酗酒的人是一个未被充分研究的群体。一个可能对理解酗酒很重要的机制是酒精摄入的“失控”，这被假设为区分酗酒者和适度社交饮酒者的基本过程。酒精对暴饮暴食行为的影响可能部分与血清素能失调和行为冲动的潜在机制有关。但是，在大学年龄以上的酗酒者中，酒精消费和血清素失调对行为冲动的影响尚未得到测试。研究人员从社区招募了48名酗酒者（n = 48）和48名非酗酒者（n = 48），年龄在24岁至34岁之间。他们在清醒的情况下和模拟的酒精狂欢中进行研究，在血清素合成减少后，确定这些情况如何影响实验室测量的冲动。三种独特的冲动性测量方法将被用于评估在模拟酒精（或安慰剂）狂欢过程之前、期间和之后的多个时间点上的组差异。4个主要实验条件包括在L-色氨酸耗竭（减少5 -羟色胺合成）和L-色氨酸平衡控制（维持5 -羟色胺合成）后给予酒精或安慰剂。本研究的目的是确定：(1)模拟酒精狂欢是否比适度饮酒者更能增加酗酒者的冲动性；(2)血清素合成的减少在多大程度上影响了暴饮暴食者和适度饮酒者的冲动性，以及这些减少是如何影响模拟暴饮暴食中酒精引起的冲动性的。第二个目的是确定在初始“启动”酒精剂量后观察到的冲动性变化与随后消费额外酒精的选择之间的关系。这个次要目标包括评估各组在“启动”酒精剂量之前和之后的冲动性测量差异，随后是一段时间的随意饮酒。这些目标旨在研究酒精和个人潜在的生物状态（即血清素合成减少）如何影响“失控”（即冲动），这被认为是导致暴食发作的原因。这项研究的创新和临床意义在于，它以新颖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与酗酒流行病学特征之间的差距。在这样做的过程中，我们将澄清机制的作用，假设有助于维持暴食发作。

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.