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

酗酒：冲动控制破坏和 5-HT 作为潜在机制

• 批准号: 8006422
• 负责人: Nathalie Hill-Kapturczak
• 金额: $ 33.9万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-16 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8006422
• 关键词: Abstinence; Address; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; Animal Model; Behavior; Behavioral; Biological; Biological Factors; Blood alcohol level measurement; Cognitive; Communities; Data; Development; Dose; Ensure; Environment; Epidemiology; Equilibrium; Exhibits; Heavy Drinking; Hour; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Informal Social Control; Intoxication; Laboratories; Link; Literature; Maintenance; Measures; Methodology; National Institute on Alcohol Abuse and Alcoholism; Patient Self-Report; Placebo Effect; Placebos; Population; Procedures; Process; Production; Public Health; Recruitment Activity; Relative (related person); Research; Research Personnel; Role; Serotonin; Simulate; Societies; Testing; Time; Tryptophan; Woman; Work; alcohol effect; alcohol use disorder; behavior measurement; binge drinker; binge drinking; binge type behavior; clinically significant; college; design; drinking; innovation; men; novel; public health relevance; sobriety; social; trait; university student; Abstinence; Address; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; Animal Model; Behavior; Behavioral; Biological; Biological Factors; Blood alcohol level measurement; Cognitive; Communities; Data; Development; Dose; Ensure; Environment; Epidemiology; Equilibrium; Exhibits; Heavy Drinking; Hour; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Informal Social Control; Intoxication; Laboratories; Link; Literature; Maintenance; Measures; Methodology; National Institute on Alcohol Abuse and Alcoholism; Patient Self-Report; Placebo Effect; Placebos; Population; Procedures; Process; Production; Public Health; Recruitment Activity; Relative (related person); Research; Research Personnel; Role; Serotonin; Simulate; Societies; Testing; Time; Tryptophan; Woman; Work; alcohol effect; alcohol use disorder; behavior measurement; binge drinker; binge drinking; binge type behavior; clinically significant; college; design; drinking; innovation; men; novel; public health relevance; sobriety; social; trait; university student

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.

描述（由申请人提供）：本研究的目的是确定暴饮暴食的成年人如何受到模拟酒精暴饮暴食的差异影响和降低5-羟色胺合成的影响。与温和的社交饮酒不同，暴饮暴食涉及戒酒时期分隔的大量饮酒事件。许多大学生进行暴饮暴食，这一直是大多数研究的重点。但是，大多数狂热的饮酒者不是大学生，而那些在大学年以外的人继续行为的人是一个研究的群体。可能对了解酒精饮料很重要的一种机制是对酒精摄入量的“失去控制”，这是一个基本过程，它将暴饮暴食与从事适度社交饮酒的人区分开来。酒精对折断行为的影响可能部分与血清素能功能障碍和行为冲动的潜在机制有关。但是，尚未测试饮酒和5-羟色胺失调对大学时代以上暴饮暴食者行为冲动的影响。在这里，将从社区招募24至34岁的狂饮（n = 48）和非暴力（n = 48）饮酒者，并在降低5-羟色胺合成后清醒和模拟的酒精狂饮中进行了研究，以确定这些条件如何影响实验室抑制冲动。冲动性的三种独特度量将用于评估在模拟酒精（或安慰剂）暴饮暴食之前，之中和之后的多个时间点的群体差异。 4个主要的实验条件包括在L-色氨酸耗竭后（血清素合成减少）和L-色氨酸平衡对照（维持5-羟色胺合成）后施用的酒精或安慰剂。这项研究的目的是确定：（1）模拟的酒精暴饮暴食是否比中度饮酒者更多地增加了暴饮暴食者的冲动； （2）5-羟色胺合成的降低在多大程度上会影响暴饮暴食者和中等饮酒者的冲动性，以及这些减少的饮酒方式如何影响模拟的暴饮暴食期间酒精引起的冲动性。第二个目的是确定初始“启动”酒精剂量后在冲动性中观察到的变化如何与随后的食用额外酒精相关的选择。次要目的包括在“启动”酒精剂量之前和之后评估冲动性度量的群体差异，然后进行一次多余的酒精消耗。这些目的旨在研究“失去控制”（即冲动性）如何受酒精和个人的潜在生物学状态（即5-羟色胺合成）的影响，这些生物学是有助于发作的。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论，以检查研究的人群，并解决动物模型与暴饮暴食的流行病学特征之间存在的文献中的差距。为此，我们将阐明被认为有助于维持暴饮暴事的机制的作用。 公共卫生相关性：本研究解决了理解潜在生物状态的酒精和个体差异如何影响涉及暴饮暴食的行为过程的关键差距。这项研究将产生数据，以阐明冲动行为和5-羟色胺功能的作用，这是有助于维持酒精暴饮暴食的发作的机制。有了这种理解，我们可以开发旨在使用认知行为和药理策略破坏此类机制的治疗方法。