BRAIN OPIOID RECEPTORS AND COGNITION IN COCAINE ABUSE

本研究的长期目标是通过使用正电子发射断层扫描（PET）来阐明内源性系统在可卡因成瘾中的作用，通过将可卡因对mu阿片受体结合的影响与决策、记忆和风险评估的认知测试中的表现联系起来。了解维持长期滥用可卡因的因素的努力最近集中在内源性阿片样物质和阿片样物质受体的作用上。通过使用选择性配体11c -卡芬太尼，PET提供了一个机会来测量人类可卡因成瘾者服用可卡因后mu阿片受体结合的动态变化。本实验室的初步结果是有希望的：可卡因滥用者大脑几个区域的mu-阿片受体显著增加，急性可卡因可以改变mu-阿片受体结合，与实验动物的结果一致。此外，我们观察到的mu阿片受体结合的变化与欣快感和复发的测量相关。因此，本提案的具体目的是：1)通过PET成像测量慢性可卡因使用者在可卡因给药前后的区域mu阿片受体结合；2)确定可卡因给药前后区域mu阿片受体结合与参数改变认知和复发的关系。该研究设计利用PET的无创性来比较可卡因成瘾者慢性滥用后的mu阿片受体，并将PET数据与可卡因滥用和可卡因给药反应的客观和主观测量相关联。这一建议的医学意义有三个方面：进一步了解可卡因强化机制；探讨阿片受体结合调节与认知的关系；并提高我们识别可卡因滥用治疗后可能复发的病人的能力。

The long-term goal of this study is to elucidate the role of the endogenous system in cocaine addiction using positron emission tomography (PET) by correlating the effects of cocaine on mu opioid receptor binding and performance on cognitive tests of decision-making, memory, and risk assessment. Efforts to understand the factors that maintain prolonged abuse of cocaine have recently focused on the role of endogenous opioids and opioid receptors. PET provides an opportunity to measure dynamic changes in mu opioid receptor binding following cocaine administration in human cocaine addicts by the use of the mu- selective ligand, 11C-carfentanil. Preliminary results from this laboratory are promising: mu-opioid receptors in several brain regions are significantly increased in cocaine abusers and acute cocaine can change mu opioid receptor binding, in accord with results in experimental animals. Furthermore, the changes in mu opioid receptor binding we have observed are correlated with measures of euphoria and relapse. Thus, the specific aims of this proposal are to: 1) measure regional mu opioid receptor binding before and after cocaine administration in chronic cocaine users by PET imaging.; and 2) determine the relationships between regional mu opioid receptor binding before and after cocaine administration and parameters altered cognition and relapse. The proposed research design utilizes the noninvasive nature of PET to compare mu opioid receptors in cocaine addicts following chronic abuse, as well as correlating PET data with objective and subjective measures of cocaine abuse and response cocaine administration. The medical significance of this proposal is threefold: to further understanding of the mechanisms of cocaine reinforcement; to determine the relations between modulation of mu opioid receptor binding and cognition; and to improve our ability to identify patients likely to relapse following treatment for cocaine abuse.