RT Journal
A1 Brody AL, Mandelkern MA, London ED, et al
T1 CIgarette smoking saturates brain α4β2 nicotinic acetylcholine receptors
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2006
FD August 1
VO 63
IS 8
SP 907
OP 914
DO 10.1001/archpsyc.63.8.907
UL http://dx.doi.org/10.1001/archpsyc.63.8.907
AB 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 α4β2* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans.Objective 
    To determine the effect of cigarette smoking on α4β2* 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 [2½ 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 α4β2* 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 α4β2* 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 α4β2* nAChRs.Conclusions 
    Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of α4β2* nAChRs, indicating that tobacco-dependent smokers maintain α4β2* nAChR saturation throughout the day. Because prolonged binding of nicotine to α4β2* 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.