Behavioral Models of Impulsivity: ETOH and 5-HT Effects

描述(申请人提供)：建议进行一系列实验，考察酒精和5-羟色胺操作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。为了确定这些手法的时程效应，将在药物干预前后定期对健康男性和女性进行评估。为了确定快速决策和奖赏导向模型是否受到酒精和/或5-羟色胺操作的不同影响，每个参与者都将体验所有的药理条件(重复测量设计)。在实验1中，我们将考察酒精对行为冲动的剂量效应。在实验2中，我们将检测L-色氨酸负荷和耗竭(改变中枢神经系统5-羟色胺水平)对行为冲动的剂量效应。在实验3中，我们将考察酒精和L-色氨酸手法对行为冲动的交互作用。这些研究的目的是确定：(1)酒精(使用0.00、0.25、0.50、0.75和1.00g/kg酒精)对快速决策和奖赏导向冲动模型的剂量依赖效应；(2)L-色氨酸手法(使用耗尽、负荷和平衡氨基酸饮料混合物)对快速决策和奖励导向冲动模型的剂量依赖效应；(3)L-色氨酸手法引起的生物状态变化如何缓解对酒精行为效应的易感性；(4)不同的冲动成分(快速决策模型和奖励导向模型)如何受到酒精和L-色氨酸操作的不同影响；(5)这些行为模型上的基线反应是如何相互关联的(解释共同和唯一的方差)以及与冲动的自我报告测量之间的关系。总之，这些研究将提供重要的信息，有助于理解酒精和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。这将提供证据，证明5-羟色胺可能是酒精诱导的行为冲动的调节因素。这些研究将作为进一步探索酒精的行为效应如何影响冲动的潜在机制，以及哪些因素导致饮酒后冲动行为的个体差异的基础。

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.