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: 8197680
• 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 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197680
• 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

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酗酒的成年人如何受到模拟酒精狂欢和5-羟色胺合成减少的不同影响。与适度的社交饮酒不同，暴饮暴食涉及到大量饮酒，并被禁欲期所分隔。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”，这被假设为是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酒精能失调和行为冲动的潜在机制有关。但是，饮酒和5-羟色胺失调对大学年龄以上酗酒者行为冲动的影响还没有得到测试。在这里，酗酒（n = 48）和非酗酒（n = 48）饮酒者，年龄24至34岁，将从社区招募和研究，而清醒和在模拟酒精狂欢后，血清素合成减少，以确定这些条件如何影响实验室测量的冲动。将使用三种独特的冲动性指标评估模拟酒精（或安慰剂）狂欢程序之前、期间和之后多个时间点的组间差异。4种主要实验条件包括在L-色氨酸消耗（减少的5-羟色胺合成）后和L-色氨酸平衡控制（维持的5-羟色胺合成）后施用的酒精或安慰剂。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）5-羟色胺合成的减少在多大程度上影响酗酒者和适度饮酒者的冲动性，以及这些减少在模拟狂欢期间如何影响酒精诱导的冲动性。次要目的是确定初始“启动”剂量酒精后观察到的冲动性变化与随后消费额外酒精的选择有何关系。这个次要目的包括评估组的冲动性措施的差异之前和之后的“启动”剂量的酒精，然后由一个会议的自由饮酒。这些目标旨在研究“失去控制”（即，冲动性）受酒精和个体的潜在生物状态（即，血清素合成减少），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学，以研究未充分研究的人群，并解决了文献中存在的动物模型和酗酒流行病学特征之间的差距。在这样做的过程中，我们将澄清的作用机制假设为有助于维持一个狂欢发作。 公共卫生关系：这项研究解决了理解酒精和潜在生物状态的个体差异如何影响酗酒行为过程的关键差距。这项研究将产生数据，以澄清冲动行为和血清素功能的作用，有助于维持酗酒发作的机制。有了这种理解，我们可以开发旨在使用认知行为和药理学策略破坏这种机制的治疗方法。