Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence

描述(由申请人提供)：以前关于可卡因依赖的研究试图确定积极治疗反应的预测因素，并侧重于人格特征、认知能力和共病。在该奖项的第一个周期中，我们小组调查了神经化学的RLE在对可卡因依赖的成熟行为治疗成功和失败中的作用。应用正电子发射断层扫描(PET)和放射性示踪剂[11C]拉氯普利，测定了寻求治疗的可卡因依赖者的D2/3受体结合电位(BPND)和刺激剂诱导的[11C]拉氯普利置换(BPND)。这些扫描是在受试者接受为期24周的积极强化(代金券激励)的行为治疗之前进行的。结果显示，与复发者相比，对治疗有反应的受试者的两项PET结果指标都有所增加。此外，BPND和BPND在治疗应答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，低多巴胺传递与治疗反应差的可能性更大，治疗应答者可能具有完整的多巴胺信号。这一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效者中所见的多巴胺传递缺陷的理解。第一个目标将是复制第一周期中使用[11C]拉氯普利和刺激性挑战的发现。为了 为了更好地描述多巴胺信号的缺陷，还将使用放射性示踪剂[18F]DOPA进行PET扫描，它提供了突触前多巴胺合成和存储的测量方法。此外，还将进行功能磁共振成像扫描，以探测奖励系统。综合起来，这些成像研究将提供对纹状体多巴胺传递和奖赏通路激活的差异的理解，这些差异将可卡因依赖患者与复发者区分开来，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.