THE EFFECTS OF ALCOHOL AND/OR L-TRYPTOPHAN ON BEHAVIOR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究是一系列实验中的第三个，这些实验考察了酒精和5-羟色胺操纵对两种截然不同的行为冲动模型（快速决策和奖励导向）的单独和综合影响。 L-色氨酸操作（负荷和消耗）已被证明会改变循环L-色氨酸（神经递质5-羟色胺的前体），随后暂时改变中枢神经系统5-羟色胺水平。 为了确定酒精和L-色氨酸操作的时程效应，将在药物干预前后定期评价健康男性和女性。 为了确定快速决策和奖励导向模型是否受到酒精和/或5-羟色胺操纵的不同影响，每位参与者将经历所有药理学条件（重复测量设计）。 在该系列的前两项研究中，我们研究了单独使用酒精（实验1）和单独使用L-色氨酸（实验2）对行为冲动的剂量效应。 本系列实验1和2的数据收集已经完成。 实验1的初步结果目前正在印刷中，实验2的数据尚未进行分析。 在这一系列的最后一项研究中，实验3，我们将研究酒精和L-色氨酸操纵行为冲动的相互作用。 本研究的目的是确定：（1）由L-色氨酸操纵产生的生物状态变化如何减轻对酒精行为影响的脆弱性;（2）冲动性的不同成分如何影响酒精的行为。（快速决策和奖励导向模型）受到酒精和L-色氨酸操纵的不同影响;以及（3）这些行为模型的基线反应如何相互关联（解释共享和独特的方差）以及自我报告的冲动性测量。 结合实验1和2，这第三项研究的结果将产生重要的信息，以了解酒精和L-色氨酸之间的关系，以及它们对人类冲动行为的单独和综合影响。 这将提供证据表明，血清素可能是酒精诱导的行为冲动的调节因素。 这些研究将为进一步探索酒精的行为效应如何影响冲动性的潜在机制以及哪些因素导致饮酒后冲动行为的个体差异奠定基础。 这对酒精相关行为障碍的病因学和这些障碍的治疗/预防策略的发展都有影响。

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. This study is the third in a series of experiments examining both the separate and the combined effects of alcohol and serotonin manipulations on two categorically distinct models of behavioral impulsivity (rapid-decision and reward-directed). L-tryptophan manipulations (loading and depletion) have been shown to alter circulating L-tryptophan (precursor of the neurotransmitter serotonin) and subsequently temporarily alter central nervous system serotonin levels. To identify the time-course effects of alcohol and L-tryptophan manipulations, healthy men and women will be evaluated at periodic intervals before and after pharmacological intervention. To determine whether rapid-decision and reward-directed models are differentially affected by alcohol and/or serotonin manipulations, each participant will experience all pharmacological conditions (repeated-measures design). In the first two studies of the series, we examined the dose effects of alcohol alone (Experiment 1) and of L-tryptophan manipulations alone (Experiment 2) on behavioral impulsivity. Data collection for Experiments 1 and 2 of this series has been completed. The primary results from Experiment 1 are currently in press, and data from Experiment 2 have not yet been analyzed. In this last study of the series, Experiment 3, we will examine the interactive effects of alcohol and L-tryptophan manipulation on behavioral impulsivity. The aims of this study are to determine: (1) how a biological state change produced by L-tryptophan manipulation can moderate vulnerability to the behavioral effects of alcohol; (2) how different components of impulsivity (rapid-decision and reward-directed models) are differentially affected by the alcohol and L-tryptophan manipulations; and (3) how baseline responding on these behavioral models relates to one another (accounting for shared and unique variance) and to self-report measures of impulsivity. Combined with Experiments 1 and 2, results of this third study will yield information important to understanding the relationship between alcohol and L-tryptophan and their individual and combined effects on human impulsive behavior. This will provide evidence that serotonin may act as a moderating factor for alcohol-induced behavioral impulsivity. These studies will serve as a basis for further exploration of how the behavioral effects of alcohol impact underlying mechanisms of impulsivity and what factors contribute to the individual differences observed in impulsive behavior after alcohol consumption. This has implications for both the etiology of alcohol-related behavioral disorders and the development of treatments/prevention strategies for these disorders.