COCAINE ADDICTION -- ALTERATIONS IN REWARD CIRCUITRY

描述：(申请人提供) 这项题为“可卡因成瘾：绘制奖赏变化图”的提案 电路，是响应RFA提交的NIDA R01的请求 《成瘾过程的认知方法》(RFA DA-01-001)。研究奖赏 在人类的回路中，研究人员已经开发出多种药物输注 用于功能磁学的方案和认知神经科学研究 磁共振成像(FMRI)。这份R01研究提案要求两个基本原则 问题：(1)是否有一个共同的电路过程来奖励期望和奖励？ 不同奖励类别的结果信息，以及(2)如何 药物依赖受试者与可卡因依赖受试者的回路功能不同 不同类别的奖励？为了解决这些问题，这项提案 概述了一种策略，以评估奖励电路的功能 三种不同奖励类别的期望和奖励结果 刺激，即药物(吗啡)、金钱和社会奖励。它 进一步寻求在匹配的队列中比较该电路的功能 药物依赖者和健康志愿者。建议进行的实验 已经在不同的健康人群中成功地进行了试验 对照，并在可卡因依赖受试者中进行试点。这些研究表明 伏隔核，杏仁核， 基底前脑的豆状核下延伸的杏仁核、腹侧被盖和 关于奖赏期望和奖赏结果的眼眶回。 具体目标1旨在评估功能磁共振反应的一致性 关于相同个体内的奖励期望和奖励结果 获得三种不同类别的奖励。这些奖励包括 非药物形式的低剂量吗啡注射的药理奖励 奖励形式为金钱，社会奖励形式为美丽VS。 普通人的脸。具体目标2-4将这些实验中的每一个应用于匹配的 评估奖励的可卡因依赖者和健康对照组的队列 预期信息和结果处理过程中的回路差异 组之间的信息。通过这些实验，可以预测到 非药物奖励的奖励回路功能将被削弱 药物依赖的受试者与健康志愿者相比，这一点 更改将在预期系统处理中最为明显 有关奖励刺激的概率信息。

DESCRIPTION: (provided by applicant) This proposal, entitled "Cocaine addiction: Mapping alterations in reward circuitry," is a request for a NIDA R01 submitted in response to the RFA "Cognitive Approaches to Addictive Processes (RFA DA-01-001). To study reward circuitry in humans, the investigators have developed multiple drug infusion protocols and cognitive neuroscience studies for use with functional magnetic resonance imaging (fMRI). This R01 research proposal asks two fundamental questions: (1) Does a common circuitry process reward expectancy and reward outcome information across distinct categories of reward, and (2) How does this circuitry function differently in drug naive vs. cocaine dependent subjects for distinct categories of reward? To address these questions, this proposal outlines a strategy to evaluate the function of reward circuitry with regard to expectancy and reward outcome across three distinct categories of rewarding stimuli, namely pharmacological (morphine), monetary, and social reward. It further seeks to compare the function of this circuitry across matched cohorts of drug dependent subjects and healthy volunteers. The experiments proposed have already been successfully performed in separate cohorts of healthy controls, and piloted in cocaine dependent subjects. These studies demonstrate unique patterns of activation for the nucleus accumbens, amygdala, sublenticular extended amygdala of the basal forebrain, ventral tegmentum, and orbital gyrus with regard to reward expectancy and reward outcome. Specific Aim 1 is designed to evaluate the consistency of the fMRI response with regard to reward expectancy and reward outcome within the same individuals receiving three distinct categories of reward. These rewards include a pharmacological reward in the form of low-dose morphine infusions, non-drug reward in the form of money, and social reward in the form of beautiful vs. average faces. Specific Aims 2-4 apply each of these experiments to matched cohorts of cocaine dependent subjects and healthy controls to evaluate reward circuitry differences in the processing of expectancy information and outcome information between groups. Across these experiments, it is predicted that reward circuitry function will be diminished for non-drug reward in drug-dependent subjects relative to healthy volunteers, and that this alteration will be most pronounced for expectancy systems processing probability information about rewarding stimuli.