Drug Abuse and Impulsivity: Tests of Animal Models

这个项目调查“冲动”作为药物滥用的诱发因素。药物滥用研究人员广泛研究了促进药物寻求行为的“奖励相关”因素，包括对药物的无条件和条件积极情感反应，而忽略了通常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使用毒品方面，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足够的实验室模型。本研究的主要目的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与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”并不是指一个单一的过程或特征。相反，几个不同的行为过程似乎构成了“冲动行为”这一宽泛类别的基础。导致冲动行为的一个过程是，人们对更小、更直接的奖励的偏好超过了更大的延迟奖励，这是用延迟折扣任务来衡量的。第二个过程对应于无法抑制（停止）阳性反应。这被称为行为抑制，用停止任务来测量。我们已经确定了第三个新的过程，它与注意力有关。注意力障碍与药物滥用的关系尚未得到广泛研究；持续的注意力可能对自我控制很重要，尤其是在戒除吸毒行为的时期。拟议的项目将使用非人类冲动性的实验室模型来确定可卡因自我管理和冲动性之间的联系强度，通过延迟折扣和持续注意力任务来衡量。一个自我给药（SA）程序，包括获得药物服用，药物摄入的升级，药物服用的消失，最后药物服用的线索诱导恢复，这是一个模拟人类药物使用的重要特征。我们之前已经积累了关于这些任务的有希望的数据，并且提出的研究将提供重要的信息来验证特定类型的冲动行为在药物滥用中的作用。拟议的研究将提供重要的新信息，关于假定的冲动动物模型，以及这些模型预测可卡因自我给药的能力。

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.