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.
The proposed study will fill a major gap in our understanding of the neurobiology of stress and susceptibility to alcohol addiction, and will provide an integrative view on the neurobiology of the disorders with potential implications for treatment development.
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