Norepinephrine Transporter Imaging in Alchohol Dependence and Obesity (Project 8

描述(由申请人提供)：来自不同学科的证据表明，急性和慢性应激相关机制在成瘾的发展和慢性、复发性成瘾中发挥重要作用。这些大脑应激系统，包括中枢和外周儿茶酚胺能系统或内源性大麻(ECB)系统，是相互关联的，两者都与成瘾行为的发展有关。为了更好地了解NE和ECB系统在酒精依赖中的相对作用，我们建议在酒精依赖患者安静状态下，分别使用[11C]MRB和[11C]Omar以及高分辨率研究断层扫描的正电子发射断层扫描来研究Net和Cb1受体在酒精依赖患者脑中的作用。为了了解ECB在调节酒精提示诱导的渴求和调节应激反应中的作用，我们建议使用选择性CBI受体放射性配基[11C]Omar和PET在体内研究酒精依赖患者在中性条件和应激暴露期间的CB1受体。我们建议对已经在进行的项目中招募的酒精依赖患者进行研究。补充将分两个阶段完成：第一阶段]酒精依赖患者(N=8)和对照组(N=8)在静息条件下的CB1PET研究；第二阶段]在中性放松体验和酒精线索暴露操作期间扫描酒精依赖患者(N=6)和单独匹配的对照组(N=6)，这些研究使用[11C]OMAR和PET按随机顺序给予。在PET成像过程中，将重复收集血浆ECB浓度和行为分级，并将其与大脑GB表达相关联。

DESCRIPTION (provided by applicant): Evidence from different disciplines suggests that acute and chronic stress-related mechanisms play an important role in the development of and the chronic, relapsing nature of addiction. These brain stress systems, including the central and peripheral catecholaminergic systems or endocannabinoid (eCB) systems, are linked to each other and both are implicated in the development of addictive behaviors. To better understand the relative contributions of NE and eCB systems in alcohol dependence, we propose to study both, the role of NET and CB1 receptor in the brain of alcohol dependent patients under resting conditions using (S,S)-[11C]MRB and [11C]OMAR, respectively and positron emission tomography (PET) on a high resolution research tomograph (HRRT). To understand the role of eCB in modulating alcohol cue induced craving and regulation of stress responses, we propose to study the CB1 receptor in vivo in patients with alcohol dependence during neutral conditions and during stress exposure using the selective CBi receptor radioligand [11C]OMAR and PET. We propose to study alcohol dependent patients who are recruited for the already ongoing project. The supplement Will be completed in 2 phases: phase 1] CB1 PET study in alcohol dependent patients (N=8) and controls (N=8) under resting conditions; followed by phase 2] to scan alcohol dependent patients (N=6) and individually matched controls (N=6) during neutral-relaxing experiences and during an alcohol cue exposure manipulation which are given in randomized order using [11C] OMAR and PET. Plasma eCB concentrations and behavioral ratings will be collected repeatedly during the PET imaging sessions and correlated with brain GB, expression.