COCAINE ADDICTION -- ALTERATIONS IN REWARD CIRCUITRY

描述：（申请人提供） 这项名为“可卡因成瘾： 电路”是响应RFA提交的NIDA R 01请求 成瘾过程的认知方法（RFA DA-01-001）。学习奖励 研究人员开发了多种药物输注 用于功能性磁共振成像的方案和认知神经科学研究 共振成像（fMRI）。R 01研究方案提出了两个基本问题 问题：（1）一个共同的电路过程是否奖励期望和奖励 不同奖励类别的结果信息，以及（2）这是如何 在未使用过药物的受试者与可卡因依赖受试者中， 不同类别的奖励？为了解决这些问题，该提案 概述了一种策略，以评估奖励电路的功能， 预期和奖励结果在三个不同类别的奖励 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 药物依赖受试者和健康志愿者。提出的实验 已经在不同的健康队列中成功地进行了 对照组，并在可卡因依赖受试者中进行试点。这些研究证明 杏仁核，杏仁核， 基底前脑的豆状核下延伸杏仁核，腹侧被盖，和 关于奖励期望和奖励结果的眶回。 具体目标1旨在评估fMRI反应的一致性 关于同一个体的奖励期望和奖励结果 获得三种不同的奖励。这些奖励包括 以低剂量吗啡输注形式的药理学奖励，非药物 以金钱形式的奖励，以及以美丽与美丽的形式的社会奖励。 平均脸具体目标2-4将这些实验中的每一个应用于匹配的 可卡因依赖性受试者和健康对照的队列以评估奖励 期望信息和结果加工中的回路差异 组之间的信息。在这些实验中，预测 奖励电路功能将减少非药物奖励， 药物依赖受试者相对于健康志愿者， 预期系统处理的变化将最为明显 关于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.