Drug Abuse and Impulsivity : Tests of Animal Models

这些研究旨在促进我们对冲动行为及其与药物滥用关系的理解，即。)开发有效的冲动行为动物模型，并将不同的冲动概念付诸实施，II。)研究急性和长期接触滥用药物甲基苯丙胺(冰毒)如何影响冲动行为，III。)研究神经递质系统多巴胺(DA)和5-羟色胺(5-HT)在冲动行为中的作用，以及iv.)研究5-羟色胺和多巴胺在冰毒对冲动行为影响中的作用。冲动是一个复杂的概念，指的是一系列不同的行为，已经在几个实验室程序中进行了模拟。然而，很少有研究评估不同衡量标准之间的关系。我们将研究5种行为程序，它们被认为是模拟大鼠冲动行为的重要方面。其中两项任务衡量的是贴现，或者说对直接的、延迟的或确定的、不确定的积极结果的偏好。第三个任务是测量动物等待延迟的大笔奖励的能力，当小奖励立即可用时。第四项任务是通过衡量对安全的小回报与高风险的大回报的偏好来衡量“冒险程度”，后者有时会受到惩罚。最后一步是测量老鼠停止(抑制)正在进行的强势反应的能力。我们计划研究急性和长期接触甲基苯丙胺的影响。我们计划研究5-羟色胺和多巴胺对冲动的作用以及甲基苯丙胺的影响。这个项目是与另一个使用人类的项目并行进行的。老鼠和人类的研究结果将被比较，以检查行为过程中物种之间的一致性，并评估老鼠模型对人类行为的有效性。总之，建议的研究将促进我们对调节冲动行为的行为和神经过程，以及滥用药物对这些行为的影响的理解。

These studies are designed to advance our understanding of impulsive behavior and its relation to drug abuse by, i.) developing valid animal models of impulsive behavior and operationalizing different concepts of impulsivity, ii.) studying how both acute and chronic exposure to the drug of abuse methamphetamine (METH) affects impulsive behavior, iii.) studying the roles the neurotransmitter systems dopamine (DA) and serotonin (5HT) in impulsive behavior, and iv.) studying the roles of 5HT and DA in mediating the effects of METH on impulsive behavior. Impulsivity is a complex concept that refers to a range of different behaviors, and has been modeled in several laboratory procedures. However, few studies have assessed the relationships among the different measures. We will investigate 5 behavioral procedures that are thought to model important aspects of impulsive behavior in rats. Two of the tasks measure discounting, or preference for immediate vs delayed or certain vs uncertain positive consequences. A third task measures the animals' ability to wait for a delayed large reward when a small reward is available immediately. A fourth task measures "risk taking" by measuring preference for a safe small rewards vs risky large rewards which are sometimes followed by punishment. The final procedure measures the ability of the rat to stop (inhibit) an ongoing prepotent response. We plan to study the effects of both acute and chronic exposure to methamphetamine. We plan to investigate the role of serotonin and dopamine on impulsivity and on the effects of methamphetamine. This project is being conducted in parallel to a separate project using humans. The results of the rat and human studies will be compared to examine concordance between species in the behavioral processes, and to assess the validity of the rat models to human behavior. In sum, the proposed studies will advance our understanding of the behavioral and neural processes mediating impulsive behaviors, and of the effect of drugs of abuse on these behaviors.