Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors.

Journal Article (Journal Article)

CONTEXT: 2-[18F]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 alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans. OBJECTIVE: To determine the effect of cigarette smoking on alpha 4 beta 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 alpha 4 beta 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 alpha 4 beta 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 alpha 4 beta 2* nAChRs. CONCLUSIONS: Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of alpha 4 beta 2* nAChRs, indicating that tobacco-dependent smokers maintain alpha 4 beta 2* nAChR saturation throughout the day. Because prolonged binding of nicotine to alpha 4 beta 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.

Full Text

Duke Authors

Cited Authors

  • Brody, AL; Mandelkern, MA; London, ED; Olmstead, RE; Farahi, J; Scheibal, D; Jou, J; Allen, V; Tiongson, E; Chefer, SI; Koren, AO; Mukhin, AG

Published Date

  • August 2006

Published In

Volume / Issue

  • 63 / 8

Start / End Page

  • 907 - 915

PubMed ID

  • 16894067

Pubmed Central ID

  • PMC2773659

International Standard Serial Number (ISSN)

  • 0003-990X

Digital Object Identifier (DOI)

  • 10.1001/archpsyc.63.8.907


  • eng

Conference Location

  • United States