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）的单独和组合影响。为了确定这些操作的时程效应，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）。在实验1中，我们将研究酒精对行为冲动的剂量效应。在实验2中，我们将研究L-色氨酸负荷和消耗（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，我们将研究酒精和L-色氨酸操作对行为冲动的交互作用。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克/公斤的酒精）的快速决策和奖励导向模型的冲动;（2）L-色氨酸操作的剂量依赖性效应（使用消耗，加载，和平衡的氨基酸饮料混合物）的快速决策和奖励导向模型的冲动;（3）L-色氨酸操纵产生的生物状态变化如何调节对酒精行为影响的脆弱性;（4）冲动的不同成分（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（5）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。总之，这些研究将产生重要的信息，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，血清素可能作为一个中介因素，酒精诱导的行为冲动。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。

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 modulate 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 mediating 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.