Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence

描述（由申请人提供）：以前的可卡因依赖研究试图确定积极治疗反应的预测因素，并集中在人格特征、认知能力和合并症上。在这个奖项的第一个周期中，我们的小组调查了神经化学在对可卡因依赖的一种成熟的行为治疗的成功和失败反应中的作用。利用正电子发射断层扫描（PET）和放射性示踪剂[11C]拉氯pride，我们测量了寻求治疗的可卡因依赖受试者D2/3受体结合电位（BPND）和兴奋剂诱导的[11C]拉氯pride位移（¿BPND）。扫描是在受试者接受为期24周的正强化（代金券激励）行为治疗之前进行的。结果显示，与复发的受试者相比，对治疗有反应的受试者的两项PET结果测量都增加了。此外，BPND和¿BPND在治疗反应者和一组匹配的健康对照组之间没有差异。因此，这些结果表明，低多巴胺传递与较差治疗反应的可能性较大有关，并且治疗应答者可能具有完整的多巴胺信号。这项竞争性更新的目标是利用成像技术进一步扩大我们对治疗无反应者中多巴胺传递缺陷的理解。第一个目标将是复制周期1中[11C]raclopride和兴奋剂挑战的发现。为了…

DESCRIPTION (provided by applicant): Previous studies of cocaine dependence have sought to identify predictors of a positive treatment response, and have focused on personality traits, cognitive ability, and co-morbidity. In the first cycle of this award, our group investigated the rle of neurochemistry in success and failure to respond to a well-established behavioral treatment for cocaine dependence. Using Positron Emission Tomography (PET) and the radiotracer [11C]raclopride, we measured both D2/3 receptor binding potential (BPND) and stimulant-induced [11C]raclopride displacement (¿BPND) in treatment-seeking cocaine dependent subjects. The scans were performed prior to subjects receiving a behavioral treatment that uses positive reinforcement (voucher incentives) for 24 weeks. The results showed that both PET outcome measures were increased in the subjects who responded to treatment compared to those who relapsed. In addition, both BPND and ¿BPND did not differ between the treatment responders and a group of matched healthy controls. Thus, these results suggest that low dopamine transmission is associated with a greater likelihood of a poor treatment response, and that treatment responders may have intact dopamine signaling. The goal of this competing renewal is to use imaging to further expand our understanding of the deficit of dopamine transmission seen in treatment non-responders. The first goal will be to replicate the finding seen in cycle one with [11C]raclopride and a stimulant challenge. In order to better characterize the deficit in dopamine signaling, PET scans will be also performed with the radiotracer [18F]DOPA, which provides a measure of pre-synaptic dopamine synthesis and storage. In addition, fMRI scans will be performed to probe the reward system. Combined, these imaging studies will provide an understanding of the differences in striatal dopamine transmission and activation of reward pathways that differentiate cocaine dependent subjects who respond to treatment compared to those who relapse, and can be used to direct future treatment development.