Treatments for Nicotine Dependence: Brain Mechanisms

描述（由申请人提供）： 尽管有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%。由于渴望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可能途径是通过更好地了解当前成功治疗的神经生物学底物，以减少渴望和吸烟。 我们小组最近的脑成像工作表明，重度吸烟者暴露于香烟相关（与中性相比）的线索，会导致跨越中线的前扣带回和左后眶额皮质的渴望强度和正常化代谢增加。此外，香烟渴望的强度与双侧眶额皮层、背外侧前额叶皮层、前额叶皮层和右侧躯体感觉皮层的相对代谢呈显著正相关。这些发现与对其他药物（可卡因、鸦片和酒精）产生依赖的渴望的研究一致。 在这项提案中，18F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）将被用来评估区域的大脑代谢与烟瘾之前和之后的两种不同形式的尼古丁依赖治疗，以检查这些治疗的大脑机制。符合尼古丁依赖完整DSM-IV标准的受试者将在接受盐酸安非他酮治疗之前和之后接受2次FDG-PET扫描（一次在暴露于香烟相关线索期间，另一次在暴露于中性线索期间），无需伴随咨询、结构化实践团体咨询（使用复发预防技术），无需伴随药物或药丸安慰剂。 本研究的目标是：（1）确定从用盐酸安非他酮、实用团体咨询或安慰剂治疗前到治疗后，在呈现与香烟相关的线索期间，局部脑代谢活化的变化，（2）确定从用盐酸安非他酮、实用团体咨询或安慰剂治疗前到治疗后，线索诱导的香烟渴望的变化，并确定线索诱导的渴望变化的大脑代谢相关性，（3）确定从盐酸安非他酮或实用团体咨询治疗前到治疗后中性状态下局部代谢的变化，以及（4）确定治疗前盐酸安非他酮治疗反应的局部脑代谢预测因子和实用团体咨询。

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.