Dopamine metabolism in nicotine dependance: [18 F]FDOPA-PET and FMRI studies in smoking and detoxified subjects

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Dopamine activity as assessed with [18F]FDOPA PET has been reported to be increased in striatum of smokers compared to non-smokers. On the other hand, in detoxified alcoholic patients [18F]FDOPA uptake was negatively correlated with alcohol craving at time of the PET scan. Using PET with [18F]FDOPA as the radiotracer and FMRI, this longitudinal study in dependent smokers will explore the functional state of dopaminergic systems at various stages of smoking and its cessation and relate these states to behavioral and neuropsychological variables and clinical outcome. Dependent smokers will undergo an [18F]FDOPA PET scan either immediately after the last cigarette (n = 20) or in acute withdrawal (n = 20). They will also be investigated with FMRI employing paradigms which tap into the reward system, and cue reactivity.The control group consists of 20 non-smokers. All smokers will then be treated in an outpatient treatment program (as part of the multicenter trial of the Priority Program). Assuming a relapse (and dropout) rate of 50% after six months, the remaining subjects (n = 20) will undergo a follow-up PET and FMRI scan after that period of abstinence. It is hypothezised that dopamine activity and BOLD contrast during the FMRI paradigms is increased in smokers, decreases in acute withdrawal and returns to normal after abstinence. It is further hypothesized that relapse risk can be predicted from the baseline studies. This study is designed to explore the neurobiological basis of nicotine dependence and to determine predictors for relapse risk, which will allow for development of novel (pharmacologic) treatment approaches.