Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers

Abstract

One-third of smokers primarily use menthol cigarettes and usage of these cigarettes leads to elevated serum nicotine levels and more difficulty quitting in standard treatment programmes. Previous brain imaging studies demonstrate that smoking (without regard to cigarette type) leads to up-regulation of β2*-containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if menthol cigarette usage results in greater nAChR up-regulation than non-menthol cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41 non-menthol cigarette smokers and 51 non-smokers) underwent positron emission tomography scanning using the α4β2* nAChR radioligand 2-[18F]fluoro-A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall test of 2-FA total volume of distribution values revealed a significant between-group difference, resulting from menthol smokers having 9–28% higher α4β2* nAChR densities than non-menthol smokers across regions. In comparing the entire group of smokers to non-smokers, an overall test revealed a significant between-group difference, resulting from smokers having higher α4β2* nAChR levels in all regions studied (36–42%) other than thalamus (3%). Study results demonstrate that menthol smokers have greater up-regulation of nAChRs than non-menthol smokers. This difference is presumably related to higher nicotine exposure in menthol smokers, although other mechanisms for menthol influencing receptor density are possible. These results provide additional information about the severity of menthol cigarette use and may help explain why these smokers have more trouble quitting in standard treatment programmes.

Differences in Quit Attempts and Cigarette Smoking Abstinence Between Whites and African Americans in the United States: Literature Review and Results From the International Tobacco Control US Survey

“…53 It is possible that the biological effects of menthol cigarettes counteract these psychosocial phenomena. 67,68 For example, lower SES smokers might use mentholated cigarettes "to facilitate increased nicotine intake from fewer cigarettes where economic pressure restricts the number of cigarettes smokers can afford to purchase." 69 It is also possible that efforts to quit are undermined by erroneous beliefs that menthol cigarettes are less dangerous than nonmentholated brands.…”

Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

“…Participants were recruited using the same methodology as in our previous reports (Brody et al, 2011;Brody et al, 2013). The central inclusion criteria were current nicotine dependence and smoking 10-40 cigarettes per day.…”

“…Approximately 1 week after the initial screening session, participants underwent PET scanning with the same general abstinence and 2-FA bolus-plus-continuous-infusion PET protocol as in previous studies (Brody et al, 2009;Brody et al, 2011;Brody et al, 2013). Participants began smoking/ nicotine abstinence two nights before the pre-and posttreatment PET sessions and were monitored as described previously, so that nicotine from smoking would not compete with the radiotracer for receptor binding during scanning.…”

“…A magnetic resonance imaging (MRI) scan of the brain was obtained for each participant within a week of PET scanning with the same specifications as in our previous report (Brody et al, 2011). Blood samples were drawn during PET scanning for determinations of free, unmetabolized 2-FA and nicotine plasma levels, as described previously (Brody et al, 2013).…”

“…Previous brain imaging studies of human smokers, including a recent one by our group, have used positron emission tomography (PET) or single photon emission computed tomography to demonstrate upregulation of nAChRs in smokers compared with non-smoking controls in brain regions other than the thalamus (Brody et al, 2013;Cosgrove et al, 2009;Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008). In follow-up scanning, nAChR upregulation in smokers was found to normalize to levels of non-smokers when participants were given contingency management to maintain abstinence for roughly 3 (Mamede et al, 2007) to 12 (Cosgrove et al, 2009) weeks.…”