beta2-Nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking

Abstract

Context: 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.

Objective: 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.

Design: 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.

Setting: Academic imaging center.

Participants: 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.

Results: 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.

Conclusions: 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.

Figure 1

β₂*-nAChR availability (V_T/f_P) is shown in individual nonsmokers (open diamonds) and tobacco smokers (filled circles) at 1 day, 1 week, 2 weeks, 4 weeks, and 6-12 weeks of abstinence in the thalamus, striatum (average of caudate and putamen), cortex (average of cortical regions including parietal, frontal, anterior cingulate, temporoinsular, and occipital cortex), and cerebellum. The line in each scatter plot represents the mean value of those subjects. * indicates significant difference from control nonsmokers after Bonferroni's correction using two-sample t-tests. † indicates significant difference from 1 week abstinent smokers after Bonferroni's correction using planned post-hoc between-group comparisons subsequent to the analysis of repeated measures mixed-effects regression models including the overall effect of abstinent smoker group.

Figure 2

Mean parametric images illustrating β₂*-nAChR availability in nonsmokers and tobacco smokers at 1 day, 1 week, 2 weeks, 4 weeks, and 6-12 weeks of abstinence at similar transaxial levels of brain. The color scale is shown with red, yellow, green and blue corresponding to V_T/f_P values.