title: Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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]).
  
  
  METHODS
  Academic brain imaging center.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA. abrody@ucla.edu
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: Richard E
authors.initials: RE
authors.lastname: Olmstead
authors.forename: Judah
authors.initials: J
authors.lastname: Farahi
authors.forename: David
authors.initials: D
authors.lastname: Scheibal
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jou
authors.forename: Valerie
authors.initials: V
authors.lastname: Allen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tiongson
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Chefer
authors.forename: Andrei O
authors.initials: AO
authors.lastname: Koren
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000097:blood / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking / Q000097:blood / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000517:prevention & control; D014018:Tissue Distribution; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: C499325:2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine