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Temporal Change in Human Nicotinic Acetylcholine Receptor After Smoking Cessation: 5IA SPECT Study

¹ Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; ² Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan; and ³ Brain Function Imaging Division, Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Correspondence: For correspondence or reprints contact: Koichi Ishizu, MD, PhD, Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Sakyo, 606-8507, Kyoto, Japan. E-mail: ishizu{at}kuhp.kyoto-u.ac.jp

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 cigarette smoking cessation 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. Methods: We performed 5-¹²³I-iodo-A-85380 (¹²³I-5IA) SPECT on nonsmokers and smokers (n = 16) who had quit smoking for 4 h, 10 d, and 21 d and calculated and compared distribution volumes (Vt) of ¹²³I-5IA. Results: The binding potential of nAChRs (Vt of ¹²³I-5IA) in the brains of smokers decreased by 33.5% ± 10.5% after 4 h of smoking cessation, increased by 25.7% ± 9.2% after 10 d of smoking cessation, and decreased to the level of nonsmokers after 21 d of smoking cessation. Conclusion: Because the upregulation of the nAChRs of the smokers after chronic exposure of the nicotine was downregulated to the nonsmokers' level by around 21 d after smoking cessation, the upregulation is a temporary effect. The decrease in nicotinic receptors to nonsmoker levels may be the breaking point during the nicotine withdrawal period.

Key Words: ¹²³I-5IA • SPECT • nicotinic acetylcholine receptors • human brain • smoking withdrawal • quantitative measurement

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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