Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density

Abstract

Cigarette smoking leads to upregulation of brain nicotinic acetylcholine receptors (nAChRs), including the common α4β2* 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 α4β2* nAChRs) before and after treatment with either cognitive-behavioral therapy, bupropion HCl, or pill placebo. Specific binding volume of distribution (VS/fP), a measure proportional to α4β2* 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 VS/fP were found for the prefrontal cortex, brainstem, and cerebellum of -20 (±35), -25 (±36), and -25 (±31)%, respectively, which represented movement of VS/fP values toward values found in non-smokers (mean 58.2% normalization of receptor levels). Participants who quit smoking had significantly greater reductions in VS/fP across regions than non-quitters, and correlations were found between reductions in cigarettes per day and decreases in VS/fP 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 α4β2* 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.

Figure 1

Mean positron emission tomography (PET) images from the study sample demonstrating decreased 2-FA binding from pre- to post-treatment for the three treatment groups. Top row consists of pre-treatment scans (n=48), followed by the post-treatment mean images for the cognitive-behavioral therapy (CBT; n=16), bupropion HCl (n=18), and pill placebo (n=14) treatment groups (rows 2–4, respectively). Mean PET images were spatially normalized to a group mean magnetic resonance imaging (MRI) scan (bottom row). V_S/f_P=specific binding volume of distribution.