Neurobiology of Reward Choice

项目摘要/摘要 几十年来，可卡因滥用一直是美国国内一个主要的公共卫生问题 尽管在为其治疗制定治疗策略方面做出了巨大努力。尤其是药物 开发工作未能产生FDA批准或普遍接受的单一药物疗法 可卡因依赖。长期滥用药物的突出和有问题的后果包括持续的 在服用药物之前作为有效增强剂的天然非药物奖励的贬值 暴露，以及与毒品相关的刺激的“激励突显”增加，导致了毒品的模型 “劫持”大脑的自然奖赏系统。这项建议的目的是确定一项行为是否 改进策略包括偶尔意外地展示高价值的替代增强剂 将增加自然奖励的享乐性价值和/或激励突显，从而减少可卡因 在老鼠身上寻找。在目标1中，我们将使用可卡因与食物选择程序来确定一种稀有的， 意想不到的奖励会将偏好从可卡因转移到食物上，并改变相关的多巴胺 伏隔核内的传递。目标2将研究这种行为操纵的后果 在一种类似复发的行为模式中。

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.