β2-nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking

Abstract

Context: Available levels of nicotinic acetylcholine receptors containing the β2 subunit (β2*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in β2*-nAChR availability during 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 iodide 123-labeled 5-iodo-A-85380 ([123I]5-IA) single-photon emission computed tomography (SPECT) scans during abstinence at 1 day (n=7) and 1 (n=17), 2 (n=7), 4 (n=11), and 6 to 12 (n=6) weeks. Age-matched nonsmokers participated in a single [123I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Setting: Academic imaging center. Participants: Tobacco smokers (n=19) and an agematched nonsmoker comparison group (n=20). Main Outcome Measure: The [123I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. Results: Compared with nonsmokers, β2*-nAChR availability in the striatum, cortex, and cerebellum of smokers was not different at 1 day of abstinence, was significantly higher at 1 week of abstinence, and was not different at 4 or at 6 to 12 weeks of abstinence. In smokers, β2*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar β2*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan. Conclusions: These data suggest that higher β2*-nAChR availability persists up to 1 month of abstinence and normalizes to nonsmoker levels by 6 to 12 weeks of abstinence from tobacco smoking. These marked and persistent changes in β2*-nAChR availability may contribute to difficulties with tobacco cessation. ©2009 American Medical Association. All rights reserved.