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Cigarette Smoking Saturates Brain α4β2 Nicotinic Acetylcholine Receptors

2006; American Medical Association; Volume: 63; Issue: 8 Linguagem: Inglês

10.1001/archpsyc.63.8.907

1538-3636

Arthur L. Brody, M. Mandelkern, Edythe D. London, Richard Olmstead, Judah Farahi, David Scheibal, Jennifer Jou, Valerie Allen, Emmanuelle Tiongson, Svetlana I. Chefer, Andrei O. Koren, Alexey G. Mukhin,

Ion channel regulation and function

Context: 2-[ 18 F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380, abbreviated as 2-FA) is a recently developed radioligand that allows for visualization of brain ␣ 4 ␤ 2 * nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans.Objective: To determine the effect of cigarette smoking on ␣ 4 ␤ 2 * nAChR occupancy in tobacco-dependent smokers.Design: Fourteen 2-FA PET scanning sessions were performed.During the PET scanning sessions, subjects smoked 1 of 5 amounts (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2 1 ⁄2 to 3 cigarettes]).Setting: Academic brain imaging center.Participants: Eleven tobacco-dependent smokers (paid volunteers).Main Outcome Measure: Dose-dependent effect of smoking on occupancy of ␣ 4 ␤ 2 * nAChRs, as measured with 2-FA and PET in nAChR-rich brain regions.Results: Smoking 0.13 (1 to 2 puffs) of a cigarette resulted in 50% occupancy of ␣ 4 ␤ 2 * nAChRs for 3.1 hours after smoking.Smoking a full cigarette (or more) resulted in more than 88% receptor occupancy and was accompanied by a reduction in cigarette craving.A venous plasma nicotine concentration of 0.87 ng/mL (roughly 1 ⁄25th of the level achieved in typical daily smokers) was associated with 50% occupancy of ␣ 4 ␤ 2 * nAChRs.Conclusions: Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of ␣ 4 ␤ 2 * nAChRs, indicating that tobacco-dependent smokers maintain ␣ 4 ␤ 2 * nAChR saturation throughout the day.Because prolonged binding of nicotine to ␣ 4 ␤ 2 * nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state.