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.
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