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.
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Acknowledgements
This study was supported by the National Institute on Drug Abuse (ALB (R01 DA20872)), the Tobacco-Related Disease Research Program (ALB (19XT-0135)), and the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412 (ALB)). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
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ALB and MAM were previously co-investigators on a grant funded by Pfizer, Inc. that was unrelated to this study. AGM is a co-investigator on a grant from Phillip Morris, Inc. for research unrelated to this study. All the other authors report no biomedical financial disclosures or potential conflicts of interest.
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Brody, A., Mukhin, A., Stephanie Shulenberger et al. Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density. Neuropsychopharmacol 38, 1548–1556 (2013). https://doi.org/10.1038/npp.2013.53
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DOI: https://doi.org/10.1038/npp.2013.53
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