Behavioral Models of Impulsivity: ETOH and 5-HT Effects

描述（由申请人提供）：提出了一系列实验，将检查酒精和血清素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）的单独和联合影响。为了确定这些操作的时间过程效应，将在药物干预前后定期评估健康男性和女性。为了确定快速决策和奖励导向模型是否受到酒精和/或血清素操纵的不同影响，每个参与者将经历所有药理学条件（重复测量设计）。在实验1中，我们将检验酒精对行为冲动的剂量效应。在实验2中，我们将检查l -色氨酸负荷和消耗（改变中枢神经系统血清素水平）对行为冲动的剂量效应。在实验3中，我们将检验酒精和l -色氨酸操纵对行为冲动的相互作用。这些研究的目的是确定：(1)酒精的剂量依赖效应（使用0.00、0.25、0.50、0.75和1.00 g/kg酒精）对快速决策和冲动的奖励导向模型的影响；(2) l -色氨酸操作（使用消耗、加载和平衡氨基酸饮料混合物）对快速决策和奖励导向冲动性模型的剂量依赖性影响；(3) l -色氨酸调控产生的生物状态变化如何调节酒精对行为影响的易感性；(4)冲动的不同组成部分（快速决策和奖励导向模型）如何受到酒精和l -色氨酸操作的不同影响；(5)对这些行为模型的基线反应是如何相互关联的（考虑到共同的和独特的方差），以及冲动性的自我报告测量。总之，这些研究将为理解酒精和l -色氨酸之间的关系以及它们对人类冲动行为的单独和联合影响提供重要信息。这将为血清素可能作为酒精诱导的行为冲动的调节因素提供证据。这些研究将为进一步探索酒精对冲动行为的影响机制以及饮酒后冲动行为的个体差异的因素提供基础。

DESCRIPTION (provided by applicant): A series of experiments are proposed that will examine 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). To identify the time-course effects of these 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 Experiment 1, we will examine dose effects of alcohol on behavioral impulsivity. In Experiment 2, we will examine dose effects of L-tryptophan loading and depletion (which alter central nervous system serotonin levels) on behavioral impulsivity. In Experiment 3, we will examine the interactive effects of alcohol and L-tryptophan manipulation on behavioral impulsivity. The aims of these studies are to determine: (1) the dose-dependent effects of alcohol (using 0.00, 0.25, 0.50, 0.75, and 1.00 g/kg of alcohol) on rapid-decision and reward-directed models of impulsivity; (2) the dose-dependent effects of L-tryptophan manipulation (using depleting, loading, and balanced amino acid drink mixtures) on rapid-decision and reward-directed models of impulsivity; (3) how a biological state change produced by L-tryptophan manipulation can moderate vulnerability to the behavioral effects of alcohol; (4) how different components of impulsivity (rapid-decision and reward-directed models) are differentially affected by the alcohol and L-tryptophan manipulations; and (5) how baseline responding on these behavioral models relates to one another (accounting for shared and unique variance) and to self-report measures of impulsivity. Together, these studies 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.