Quantitative Analysis of Nicotinic Acetylcholine Receptors in Human Brain ; Effects of Aging and Smoking Cessation

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Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (-)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after smoking cessation of smoking in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. We performed [^<123>I]-5IA SPECT in non-smokers and smokers (n=16) who had quit smoking for 4 h, 10 days, and 21 days and calculated and compared distribution volumes (Vt) of [^<123>I]-5IA. The binding potential of nAChRs (Vt of the [^<123>I]-5IA) in the brains of smokers decreased by 33.5% ± 10.5% after 4 hours of smoking cessation ; increased by 25.7% ± 9.2% after 10 days of smoking cessation ; and decreased to the level of non-smokers in after 21 days of smoking cessation. Since the upregulation of the nicotinic acetylcholine receptors of the smokers after chronic exposure of the nicotine was downregulated to the non-smokers' level by around 21 days after smoking cessation, the upregulation is a temporary effect. Thus, a decrease in the number of nicotine receptors to the level in nonsmokers may be a step in overcoming nicotine dependence.