Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

The aim of this study was to determine whether standard treatments for Tobacco Dependence affect smoking-induced changes in intrasynaptic dopamine (DA) concentration. Forty-three otherwise healthy adult cigarette smokers (10 to 40 cigarettes per day) were treated with either practical group counseling (PGC) psychotherapy (n = 14), bupropion HCl (n = 14), or matching pill placebo (n = 15) (random assignment) for 8 weeks. Before and after treatment, each subject underwent a bolus-plus-continuous-infusion 11 C-raclopride positron emission tomography (PET) scanning session, during which he or she smoked a regular cigarette. The PET scanning outcome measure of interest was percent change in smoking-induced 11 C-raclopride binding potential (BP ND ) in the ventral caudate/nucleus accumbens (VCD/NAc), as an indirect measure of DA release. Although the entire study sample had a smaller mean smoking-induced reduction in VCD/ NAc BP ND after treatment (compared to before treatment), this change was highly correlated with smaller total cigarette puff volumes (and not other treatment variables). These data indicate that smoking-induced DA release is dose-dependent, and is not significantly affected by reductions in daily smoking levels or treatment type.

Cigarette smoking leads to upregulation of brain nicotinic acetylcholine receptors (nAChRs), including the common a 4 b 2 * nAChR subtype. Although a substantial percentage of smokers receive treatment for tobacco dependence with counseling and/or medication, the effect of a standard course of these treatments on nAChR upregulation has not yet been reported. In the present study, 48 otherwise healthy smokers underwent positron emission tomography (PET) scanning with the radiotracer 2-FA (for labeling a 4 b 2 * nAChRs) before and after treatment with either cognitive-behavioral therapy, bupropion HCl, or pill placebo. Specific binding volume of distribution (V S /f P ), a measure proportional to a 4 b 2 * nAChR density, was determined for regions known to have nAChR upregulation with smoking (prefrontal cortex, brainstem, and cerebellum). In the overall study sample, significant decreases in V S /f P were found for the prefrontal cortex, brainstem, and cerebellum of À 20 (±35), À 25 (±36), and À 25 (±31)%, respectively, which represented movement of V S /f P values toward values found in non-smokers (mean 58.2% normalization of receptor levels). Participants who quit smoking had significantly greater reductions in V S /f P across regions than non-quitters, and correlations were found between reductions in cigarettes per day and decreases in V S /f P for brainstem and cerebellum, but there was no between-group effect of treatment type. Thus, smoking reduction and cessation with commonly used treatments (and pill placebo) lead to decreased a 4 b 2 * nAChR densities across brain regions. Study findings could prove useful in the treatment of smokers by providing encouragement with the knowledge that decreased smoking leads to normalization of specific brain receptors.

While bupropion HCl and practical group counseling (PGC) are commonly used treatments for tobacco dependence, the effects of these treatments on brain function are not well established. For this study, 54 tobacco-dependent cigarette smokers underwent resting 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning before and after 8 weeks of treatment with bupropion HCl, PGC, or pill placebo. Using Statistical Parametric Mapping (SPM 2), changes in cerebral glucose metabolism from before to after treatment were compared between treatment groups and correlations were determined between amount of daily cigarette usage and cerebral glucose metabolism. Compared with placebo, the two active treatments (bupropion HCl and PGC) had reductions in glucose metabolism in the posterior cingulate gyrus. Further analysis suggested that PGC had a greater effect than bupropion HCl on glucose metabolism in this region. We also found positive correlations between daily cigarette use and glucose metabolism in the left occipital gyrus and parietal-temporal junction. There were no significant negative correlations between daily cigarette use and glucose metabolism. Our findings suggest that bupropion HCl and PGC reduce neural activity much as the performance of a goal-oriented task does in the default mode network of the brain, including the posterior cingulate gyrus. Thus, this study supports the theory that active treatments for tobacco dependence move the brain into a more goal-oriented state.