Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

Abstract

In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two (18)F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order--one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.

Fig. 1

Regions of interest drawn on a study subject’s magnetic resonance image for transfer onto co-registered PET scans. Images are presented from dorsal (top) to ventral (bottom). DLPFC = dorsolateral prefrontal cortex; ACC = anterior cingulate cortex; Ant = anterior; OFC = orbitofrontal cortex.

Fig. 2

Statistical parametric mapping results for the untreated smoker group alone (n=20) showing significant activation (P<0.005) of the perigenual anterior cingulate cortex (ACC) from the neutral to the cigarette-cue conditions (Panel 1). Panel 2 shows a small area of activation in the bupropion-treated group (n=17) alone. Panel 3 shows the ACC region of activation that was greater for untreated than bupropion-treated smokers.

Fig. 3

Region of interest analysis showing activation from the neutral to the cigarette-cue state of normalized left (panel 1) and right (panel 2) ventral anterior cingulate cortex (ACC) metabolism for untreated (red), but not bupropion-treated (blue), smokers. A higher mean neutral state ACC metabolic rate is seen in the bupropion-treated than the untreated group.

Fig. 4

Statistical parametric mapping analysis showing regions with significant associations (P<0.005) between subjective craving and regional metabolism for the bupropion-treated smoker group alone (n=17). These regions included the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC).