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

据报道，用[18F]FDOPA PET评估吸烟者纹状体中的多巴胺活性比不吸烟者增加。另一方面，在解毒酒精患者中[18F]， PET扫描时FDOPA摄取与酒精渴望呈负相关。使用PET和[18F]FDOPA作为放射性示踪剂和FMRI，这项对依赖吸烟者的纵向研究将探索吸烟和戒烟各阶段多巴胺能系统的功能状态，并将这些状态与行为和神经心理变量以及临床结果联系起来。依赖吸烟者将在最后一支烟后立即（n = 20）或在急性戒断时（n = 20）进行FDOPA PET扫描[18F]。他们还将使用FMRI进行调查，该模式利用奖励系统和线索反应。对照组由20名不吸烟者组成。所有吸烟者将在门诊治疗项目中接受治疗（作为优先项目多中心试验的一部分）。假设六个月后复发率为50%，剩下的受试者（n = 20）将在这段时间的戒断后接受随访的PET和FMRI扫描。假设吸烟者在FMRI范式中多巴胺活性和BOLD对比增加，急性戒断时减少，戒烟后恢复正常。进一步假设复发风险可以从基线研究中预测。本研究旨在探索尼古丁依赖的神经生物学基础，并确定复发风险的预测因素，这将允许开发新的（药物）治疗方法。

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.