Drug Abuse and Impulsivity: Tests of Animal Models

这个项目调查了“冲动”作为药物滥用的一个诱因。药物滥用研究人员广泛研究了促进药物寻觅行为的“奖赏相关”因素，包括对药物的无条件和有条件的积极情感反应，而忽略了通常会抑制或限制药物使用的“冲动相关”过程。我们认为，在决定一个人是否会吸毒时，与冲动相关的过程可能与奖励过程一样重要。缺乏对“冲动相关”因素的关注的一个原因可能是缺乏适当的实验室模型。这项研究的主要目标是开发和使用基于实验室的冲动行为测量方法来研究冲动过程和药物滥用之间的关系。我们自己的研究以及其他最近的发现表明，“冲动”并不是指单一的过程或特征。相反，有几个不同的行为过程似乎构成了“冲动行为”这一大类的基础。一个可能导致冲动行为的过程是，相对于较大的延迟奖励，更倾向于较小的、更直接的奖励，这是通过延迟折扣任务来衡量的。第二个过程对应于无法抑制(停止)优势反应。这被称为行为抑制，并使用停止任务进行测量。我们已经确定了与注意力有关的第三个新进程。注意力障碍与药物滥用的关系尚未被广泛研究；持续的注意力可能对自我控制很重要，特别是在戒毒行为期间。这个拟议的项目将使用非人类实验室的冲动模型来确定可卡因自我管理和冲动之间的联系强度，通过延迟折扣和持续的注意力任务来衡量。将使用一种自我管理(SA)程序，包括获得吸毒、增加吸毒、戒除吸毒，并最终在线索诱导下恢复吸毒，这是模拟人类吸毒的重要特征。我们之前已经积累了关于这些任务的有希望的数据，拟议的研究将提供重要的信息，证实特定类型的冲动行为在药物滥用中的作用。拟议的研究将提供有关冲动的假定动物模型以及这些模型预测可卡因自我给药的能力的重要新信息。

This project investigates “impulsivity” as a predisposing factor for drug abuse. Drug abuse researchers have extensively studied “reward-related” factors that facilitate drug-seeking behaviors, including both unconditioned and conditioned positive affective responses to drugs while ignoring “impulsivity-related” processes that normally inhibit or limit the use of drugs. We believe that processes related to impulsivity may be as important as reward processes in determining whether an individual will use drugs. One reason for the lack of attention to “impulsivity related” factors may be the lack of adequate laboratory models. The primary objective of the proposed research is to develop and use laboratory-based, behavioral measures of impulsivity to study the relationship between impulsive processes and drug abuse. Our own research as well as other recent findings indicates that “impulsivity” does not refer to a single process or trait. Instead, several distinct behavioral processes appear to underlie the broad category of “impulsive behaviors”. One process that can result in impulsive behaviors is the preference for smaller, more immediate rewards over larger delayed rewards, and it is measured using the delay discounting task. A second process corresponds to the inability to inhibit (stop) a prepotent response. This is referred to as behavioral inhibition and is measured using the Stop Task. We have identified a new, third process, which relates to attention. Impairments in attention have not been studied extensively in relation to drug abuse; sustained attention is likely to be important for self-control, particularly during periods of abstinence from drug taking behaviors. The proposed project will use non-human laboratory models of impulsivity to determine the strength of association between cocaine self-administration and impulsivity as measured by delay discounting and sustained attention tasks. A self-administration (SA) procedure which includes acquisition of drug taking, escalation of drug intake, extinction of drug taking, and finally cue-induced reinstatement of drug taking, which models important features of human drug use will be used. We have previously accumulated promising data on these tasks, and the proposed studies will provide important information validating the role of specific types of impulsive behaviors in drug abuse. The proposed studies will provide important new information concerning putative animal models of impulsivity, and the ability of these models to predict cocaine self-administration.