β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

Abstract

Context β2*-nicotinic acetylcholine receptor (β2*-nAChR) availability is higher in recently abstinent smokers compared to never smokers. Variations in β2*-nAChR availability over the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal and successful abstinence. Objective To examine changes in β2*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in β2*-nAChR availability were related to clinical features of tobacco smoking. Design Tobacco smokers participated in up to 4 [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT) scans during abstinence: 1 day (n=7), 1 week (n=17), 2 weeks (n=7), 4 weeks (n=11), and 6-12 weeks (n=6). Age-matched nonsmokers participated in 1 [123I]5-IA SPECT scan. All subjects completed 1 magnetic resonance imaging study. Setting Academic imaging center. Participants Tobacco smokers (n=19) and an age-matched nonsmoker comparison group (n=20). Main Outcome Measure [123I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. Results Compared to nonsmokers, β2*-nAChR availability in the striatum, cortex and cerebellum of smokers was not different at one day of abstinence, significantly higher at 1week of abstinence and not different at 4 or 6-12 weeks of abstinence. In smokers, at 6-12 weeks of abstinence, β2*-nAChR availability was significantly lower in the cortex and cerebellum compared to 1 week of abstinence. Additionally, cerebellar β2*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of scan. Conclusions These data suggest higher β2*-nAChR availability persists up to 1 month of abstinence, and normalizes to nonsmoker levels by 6-12 weeks of abstinence from tobacco smoking. These marked and persistent changes in β2*-nAChR availability may contribute to difficulties with tobacco cessation.

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

“…We saw a significantly longer-lasting up-regulation of nAChRs, still present 8 days following nicotine cessation in both the striatum and hippocampus, after three nicotine exposures and withdrawals. This result is consistent with a recent SPECT study that showed nicotinic receptors remained elevated in smokers for up to 12 weeks (Cosgrove et al, 2009). Therefore, our data support the idea that multiple withdrawal periods might modulate the brain response to nicotine-induced cholinergic system imbalance by long-term alteration of receptor function.…”

“…This receptor-level adaptation to repeated nicotine exposure and withdrawal may underlie some of the behavioral phenomena we observe in mice. Similarly, imaging studies in humans proposed a functional role of these up-regulated nAChRs in relapse vulnerability (Cosgrove et al, 2009). Previously, nicotine receptor regulation was only determined after cessation of chronic nicotine treatment but not following repeated withdrawals (Collins et al, 1994;Hulihan-Giblin et al, 1990;Pietila et al, 1998;Turner et al, 2011).…”

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

“…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. However, to our knowledge, no one has yet reported the effects of commonly used, standard first-line treatments for cigarette smoking on nAChR density.…”

“…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.…”

Translational Research in Nicotine Dependence

“…However, PET imaging in human smokers following different periods of abstinence suggest that this up-regulation may directly contribute to smoking relapse. Cosgrove and colleagues showed that b2-containing nAChRs remain significantly up-regulated after 1 mo of abstinence and their density was positively correlated to craving (Cosgrove et al 2009). Although correlational, this study suggests that the phenomenon of receptor upregulation could directly contribute to failed smoking cessation.…”