Neurobiology of Reward Choice

项目总结/摘要 几十年来，可卡因滥用一直是美国一个主要的公共卫生问题 尽管已经做出了大量的努力来开发用于其治疗的治疗策略。特别是药物 开发努力未能产生单一FDA批准或普遍接受的药物疗法， 可卡因依赖长期药物滥用的突出和问题性后果包括： 自然的非药物奖励贬值，这些奖励在药物之前曾作为有效的奖励发挥作用 暴露，并增加了“激励显着性”的药物相关的刺激，导致模型，药物 “劫持”大脑的自然奖励系统。本提案的目的是确定行为是否 修改策略，包括偶尔的、意外的高价值替代替代品的呈现 将增加自然奖励的享乐价值和/或动机显著性， 寻找老鼠在目标1中，我们将使用操作性可卡因与食物选择程序来确定是否存在罕见的， 意想不到的奖励将改变对可卡因的偏好反应，并改变相关的多巴胺 在丘脑核中的传输。目标2将检验这种行为操纵的后果 一个类似复发的行为模型。

Project Summary/Abstract Cocaine abuse has persisted as a major public health concern within the United States for several decades despite substantial efforts to develop therapeutic strategies for its treatment. In particular, medications development efforts have failed to yield a single FDA-approved or generally accepted pharmacotherapy for cocaine dependence. Prominent and problematic consequences of prolonged drug abuse include the persistent devaluation of natural nondrug rewards that previously functioned as effective reinforcers prior to drug exposure, and an increase in the “incentive salience” of drug-associated stimuli, leading to the model that drugs “hijack” the brain's natural reward system. The purpose of this proposal is to determine whether a behavioral modification strategy encompassing occasional, unexpected presentation of a high-value, alternate reinforcer will increase the hedonic value and/or motivational salience of a natural reward such that it will reduce cocaine seeking in rats. In Aim 1, we will use an operant cocaine vs. food choice procedure to determine whether a rare, unexpected reward will shift preferred responding from cocaine to food and alter associated dopamine transmission in the nucleus accumbens. Aim 2 will examine the consequences of this behavioral manipulation in a model of relapse-like behavior.