Treatments for Nicotine Dependence: Brain Mechanisms

描述(由申请人提供)： 尽管有治疗尼古丁依赖的新药物选择，但治疗6个月或更长时间后的戒烟率仍然相对较低，为14%至35.5%。由于烟瘾的严重程度一再与尝试戒烟的吸烟者的复发有关，因此开发更有效的尼古丁依赖治疗方法的一个可能途径是更好地了解目前成功的减少烟瘾和吸烟的治疗方法的神经生物学基础。 我们小组最近的脑成像工作表明，重度吸烟者暴露在与香烟相关的(与中性相比)线索中，会导致跨越中线和左侧后眶额叶皮质的前扣带回渴望强度和正常代谢的增加。此外，在双侧OFC、背外侧前额叶皮质、前岛叶和右侧躯体感觉皮质，吸烟渴求强度与相对代谢呈显著正相关。这些发现与对其他导致依赖的药物(可卡因、鸦片和酒精)的渴求研究是一致的。 在这项提议中，将使用18F-脱氧葡萄糖正电子发射断层扫描(FDG-PET)来评估两种不同形式的尼古丁依赖治疗前后与香烟渴求有关的大脑局部代谢，以检查这些治疗的大脑机制。完全符合DSM-IV尼古丁依赖标准的受试者将在治疗前后接受两次FDG-PET扫描(一次是在暴露于与香烟相关的线索期间，另一次是在暴露于中性线索期间)，治疗前后要么接受安非他酮HCI而不伴随咨询，要么接受结构化实用的团体咨询(使用复发预防技术)而不伴随药物，或者服用安慰剂。 本研究的目标是：(1)确定使用安非他酮、实用团体咨询或安慰剂呈现香烟相关线索的治疗前后大脑局部代谢激活的变化；(2)确定使用安非他酮、实用团体咨询或安慰剂从治疗前到治疗后线索诱导的香烟渴求的变化，并确定线索诱导的渴望变化的大脑代谢相关性。(3)确定安非他酮治疗前后中性状态下局部代谢的变化，以及(4)确定治疗前局部脑代谢预测因子对安非他酮治疗和实际团体咨询的反应。

DESCRIPTION (provided by applicant): Despite new medication options for nicotine dependence, abstinence rates after 6 months or more of treatment remain relatively low at 14 to 35.5%. Because severity of craving has repeatedly been linked with relapse in smokers attempting abstinence, a possible route to the development of more effective treatments for nicotine dependence is through a better understanding of the neurobiological substrates of current successful treatments that reduce craving and cigarette usage. Recent brain imaging work from our group demonstrates that exposure of heavy cigarette smokers to cigarette related (compared with neutral) cues results in increases in both the intensity of craving and normalized metabolism in the anterior cingulate gyrus spanning the midline and left posterior orbitofrontal cortex. Additionally, intensity of cigarette craving was significantly positively correlated with relative metabolism in the bilateral OFC, dorsolateral prefrontal cortex, anterior insula, and right somatosensory cortex. These findings are consistent with studies of craving for other drugs that produce dependence (cocaine, opiates, and alcohol). In this proposal, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) will be used to assess regional brain metabolism associated with cigarette craving both before and after two distinct forms of treatment for nicotine dependence in order to examine the brain mechanisms of these treatments. Subjects meeting full DSM-IV criteria for nicotine dependence will undergo 2 FDG-PET scans (one during exposure to cigarette-related cues and the other during exposure to neutral cues) both before and after treatment with either bupropion HCI with no concomitant counseling, structured practical group counseling (using relapse prevention techniques) with no concomitant medication, or pill placebo. The goals of this study are: (1) to determine changes in regional cerebral metabolic activation during presentation of cigarette-related cues from pre- to post- treatment with either bupropion HCI, practical group counseling, or placebo, (2) to determine changes in cue-induced cigarette craving from pre- to post- treatment with either bupropion HCI, practical group counseling, or placebo, and determine brain metabolic correlates of changes in cue-induced craving, (3) to determine changes in regional metabolism in the neutral state from pre- to post- treatment with either bupropion HCI or practical group counseling and (4) to determine pre- treatment regional brain metabolic predictors of response to bupropion HCI and practical group counseling.