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Neurobiology of Reward Choice

奖励选择的神经生物学

基本信息

批准号：
9181667
负责人：
DAVID WEINSHENKER
金额：
$ 21.89万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9181667
关键词：
Abstinence Animal Model Attenuated Back Behavior Behavior Control Behavior Therapy Behavioral Brain Chronic Clinical Cocaine Cocaine Abuse Cocaine Dependence Cues Development Dopamine Drug Addiction Drug Exposure Drug abuse Drug usage Electrodes Exhibits Exposure to Extinction (Psychology)FDA approved Female Food Goals Implant Investigation Lead Learning Measures Methods Modeling Neuroanatomy Neurobiology Neurotransmitters Nucleus Accumbens Pharmaceutical Preparations Pharmacotherapy Play Prize Procedures Public Health Rattus Relapse Research Personnel Research Project Grants Rewards Role Scanning Sex Characteristics Signal Transduction Stimulus Sucrose System Testing Therapeutic Time Training United States Variant Visual Water abstracting base carbon fiber contingency management drug of abuse effective therapy hedonic incentive salience male men&apos s group neurochemistry neurotransmission non-drug novel preference prevent reinforcer response sex stressor transmission process treatment program

项目摘要

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.

项目概要/摘要几十年来，可卡因滥用一直是美国的一个主要公共卫生问题尽管付出了大量努力来制定治疗策略。特别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。长期吸毒的突出和有问题的后果包括持续的天然非药物奖励的贬值，这些奖励在药物之前曾作为有效的强化物暴露，以及与药物相关的刺激的“激励显着性”的增加，导致了药物模型 “劫持”大脑的自然奖励系统。该提案的目的是确定行为是否修改策略包括偶尔、意外地出现高价值的替代强化物将增加自然奖励的享乐价值和/或动机显着性，从而减少可卡因在老鼠身上寻找。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稀有、意外的奖励会将偏好反应从可卡因转向食物，并改变相关的多巴胺伏隔核中的传输。目标 2 将检查这种行为操纵的后果在类似复发的行为模型中。