The present study examined the time course of changes in β2*-nAChR availability during acute and prolonged abstinence in tobacco smokers compared to nonsmokers using [123I]5-IA SPECT. The present findings demonstrate higher β2*-nAChR availability in the striatum, cerebellum and cerebral cortex in tobacco smokers at 1 week of abstinence compared to nonsmokers, but similar or lower β2*-nAChR availability to nonsmokers smokers at 1 day and 6-12 weeks of abstinence. While there is not a significant difference between β2*-nAChR availability in smokers at 2 and 4 weeks of abstinence compared to nonsmokers, there remains a robust difference, e.g., higher β2*-nAChR availability in smokers at 2 weeks (16-23%) and 4 weeks (14-18%) of abstinence in the striatum, cerebellum and cortex compared to nonsmokers, that does not return to nonsmoker levels until 6-12 weeks of abstinence (-4-5% difference). There are two primary implications to these results. First, at 1 day of abstinence there is still residual nicotine, or a pharmacologically active metabolite of nicotine, such as cotinine or nornicotine present in the brain that interferes with radiotracer binding, thus leading to the appearance of
