Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain

Abstract

Context Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger’s seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of α4β2* nAChR occupancy. Results An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P <.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain α4β2* nAChRs (1-sample t test, 2-tailed, P <.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic α4β2* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ= −0.74, P =.01). Conclusions Nicotine from SHS exposure results in substantial brain α4β2* nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.

Predictors of nicotine dependence symptoms among never-smoking adolescents: A longitudinal analysis from the Nicotine Dependence in Teens Study

“…Recent findings support this notion of pharmacological priming. Brody et al (2011) showed that SHS exposure leads to α4β2* nicotinic cholinergic receptor occupancy in non-smokers, which parallels findings of withdrawal sensations observed in tobacco-naive rats exposed to SHS . Relatedly, it is unclear whether pharmacological exposure to nicotine may partly explain established findings with social modeling.…”

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.…”

A Single Administration of Low-Dose Varenicline Saturates α4β2* Nicotinic Acetylcholine Receptors in the Human Brain

“…2-FA was synthesized as described previously (Doll et al, 1999), and the bolus plus infusion was designed to produce an approximate steady-state level of 2-FA in the brain within 4 h after injection (Brody et al, 2006(Brody et al, , 2009(Brody et al, , 2011. Lunch was provided after infusion initiation and participants continued to rest until the first PET imaging block at 1600 hours.…”

“…Blood-plasma samples were obtained for quantification of free, unmetabolized 2-FA, as previously reported (Brody et al, 2011), as well as for the measurement of nicotine, cotinine, and varenicline levels. Whole blood was collected in heparinized sealed tubes placed on ice until centrifugation; subsequently, plasma was collected and stored in polypropylene tubes.…”

“…Prolonged tobacco use is a major risk factor for a number of illnesses, including cancer, cardiovascular disease, and emphysema. The consequences of tobacco use are far reaching, influencing others through second- (Brody et al, 2011) and third-hand (Ueta et al, 2010) exposure, as well as causing developmental exposure during pregnancy (Lotfipour et al, 2009Toledo-Rodriguez et al, 2010). Given the many risks associated with tobacco use and the global consequences, it is surprising that over a billion people continue to smoke worldwide.…”