Drug Abuse and Impulsivity : Tests of Animal Models

这些研究旨在通过以下方式增进我们对冲动行为及其与药物滥用的关系的理解：(1)建立有效的冲动行为动物模型并对不同的冲动概念进行操作；(2)研究急性和慢性暴露于滥用甲基苯丙胺（冰毒）药物如何影响冲动行为；(3)研究神经递质系统多巴胺（DA）和血清素（5HT）在冲动行为中的作用。iv.研究5HT和DA在甲基安非他明对冲动行为的介导作用。冲动性是一个复杂的概念，涉及一系列不同的行为，并已在几个实验室程序中建模。然而，很少有研究评估不同测量之间的关系。我们将研究被认为是模拟大鼠冲动行为重要方面的5种行为程序。其中两个任务测量贴现，或者是对即时与延迟、确定与不确定的积极结果的偏好。第三项任务是测试动物在立即获得小奖励时等待延迟大奖励的能力。第四个任务是衡量“冒险”程度，即衡量人们对安全的小奖励和高风险的大奖励的偏好，后者有时会受到惩罚。最后一个步骤是测量大鼠停止（抑制）正在进行的阳痿反应的能力。我们计划研究急性和慢性接触甲基苯丙胺的影响。我们计划研究血清素和多巴胺在冲动中的作用以及甲基苯丙胺的作用。这个项目正在与另一个使用人类的项目并行进行。将对大鼠和人类的研究结果进行比较，以检验物种在行为过程中的一致性，并评估大鼠模型对人类行为的有效性。综上所述，本研究将促进我们对冲动行为的行为和神经过程的理解，以及药物滥用对这些行为的影响。

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.