Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence

描述（由申请人提供）：以前的可卡因依赖性研究试图确定积极治疗反应的预测因子，并侧重于人格特征，认知能力和合并症。在这个奖项的第一个周期中，我们的团队调查了神经化学在成功和失败的可卡因依赖行为治疗中的作用。使用正电子发射断层扫描（PET）和放射性示踪剂[11 C]雷氯必利，我们测量了寻求治疗的可卡因依赖受试者的D2/3受体结合电位（BPND）和兴奋剂诱导的[11 C]雷氯必利置换（<$BPND）。扫描是在受试者接受为期24周的使用正强化（代金券激励）的行为治疗之前进行的。结果显示，与复发的受试者相比，对治疗有反应的受试者的PET结局指标均增加。此外，BPND和<$BPND在治疗应答者和一组匹配的健康对照之间没有差异。因此，这些结果表明，低多巴胺传输与治疗反应不良的可能性更大相关，并且治疗反应者可能具有完整的多巴胺信号传导。这种竞争性更新的目标是使用成像来进一步扩大我们对治疗无应答者中多巴胺传递缺陷的理解。第一个目标将是复制[11 C]雷氯必利和兴奋剂挑战在第一周期中看到的发现。为了 为了更好地表征多巴胺信号传导的缺陷，还将使用放射性示踪剂[18F]DOPA进行PET扫描，其提供突触前多巴胺合成和储存的测量。此外，还将进行功能性磁共振成像扫描，以探测奖励系统。结合起来，这些成像研究将提供纹状体多巴胺传递和奖励途径激活的差异的理解，区分可卡因依赖受试者谁响应于治疗相比，那些复发，并可用于指导未来的治疗开发。

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.