Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain

Arch Gen Psychiatry. 2011 Sep;68(9):953-60. doi: 10.1001/archgenpsychiatry.2011.51. Epub 2011 May 2.


Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking.

Objective: To determine whether moderate SHS exposure results in brain α(4)β(2)* nicotinic acetylcholine receptor (nAChR) occupancy.

Design, setting, and participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[(18)F]fluoro-A-85380, or 2-FA) were used to determine α(4)β(2)* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of α(4)β(2)* nAChR occupancy.

Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F(1,22) = 42.5, P < .001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain α(4)β(2)* nAChRs (1-sample t test, 2-tailed, P < .001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic α(4)β(2)* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ = -0.74, P = .01).

Conclusions: Nicotine from SHS exposure results in substantial brain α(4)β(2)* nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Azetidines
  • Behavior, Addictive / metabolism
  • Brain / metabolism*
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nicotinic Agonists*
  • Positron-Emission Tomography / methods
  • Radioligand Assay
  • Receptors, Nicotinic / metabolism*
  • Tobacco Smoke Pollution / adverse effects*


  • A 85380
  • Azetidines
  • Fluorine Radioisotopes
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Tobacco Smoke Pollution
  • nicotinic acetylcholine receptor alpha4 subunit
  • nicotinic receptor beta2