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

Abstract

Available levels of nicotinic acetylcholine receptors containing the beta(2) subunit (beta(2)*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in beta(2)*-nAChR availability during the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal, and successful abstinence. To examine changes in beta(2)*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in beta(2)*-nAChR availability were related to clinical features of tobacco smoking. Tobacco smokers participated in up to 4 iodide 123-labeled 5-iodo-A-85380 ([(123)I]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 [(123)I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Academic imaging center. Tobacco smokers (n = 19) and an age-matched nonsmoker comparison group (n = 20). Main Outcome Measure The [(123)I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. Compared with nonsmokers, beta(2)*-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, beta(2)*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar beta(2)*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan. These data suggest that higher beta(2)*-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 beta(2)*-nAChR availability may contribute to difficulties with tobacco cessation.