Previous preclinical studies demonstrated that in chronically nicotine treated animals, nAChR levels returned to levels observed in control animals after termination of nicotine, but with variable timing ranging between 1 and 3 weeks15, 80, 81. The previous human study18 indicated a return to control levels within 21 days of abstinence; and, the current study indicates that on average, β2*-nAChR availability in recently abstinent tobacco smokers does not normalize until between 4-12 weeks, although, this is highly variable between individuals. The differences in the time course changes may be due to differences in dosing regimen, chronicity of nicotine, route of administration, metabolism between species, specificity of the radioligand, or sex and/or genetic differences in nAChR subunit expression and composition of nicotinic agonist binding sites, but taken together the results consistently highlight a return to control levels or “normalization” of the β2*-nAChR after termination of chronic nicotine. The preclinical studies support a process of prolonged normalization when we consider that 1-3 weeks is substantial in the life span of a rodent. Additionally, this prolonged normalization of the receptor is in line with
