beta2-Nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking

Arch Gen Psychiatry. 2009 Jun;66(6):666-76. doi: 10.1001/archgenpsychiatry.2009.41.

Abstract

Context: Available levels of nicotinic acetylcholine receptors containing the beta(2) subunit (beta(2)*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in beta(2)*-nAChR availability during the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal, and successful abstinence.

Objective: To examine changes in beta(2)*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in beta(2)*-nAChR availability were related to clinical features of tobacco smoking.

Design: Tobacco smokers participated in up to 4 iodide 123-labeled 5-iodo-A-85380 ([(123)I]5-IA) single-photon emission computed tomography (SPECT) scans during abstinence at 1 day (n = 7) and 1 (n = 17), 2 (n = 7), 4 (n = 11), and 6 to 12 (n = 6) weeks. Age-matched nonsmokers participated in a single [(123)I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study.

Setting: Academic imaging center.

Participants: Tobacco smokers (n = 19) and an age-matched nonsmoker comparison group (n = 20). Main Outcome Measure The [(123)I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest.

Results: Compared with nonsmokers, beta(2)*-nAChR availability in the striatum, cortex, and cerebellum of smokers was not different at 1 day of abstinence, was significantly higher at 1 week of abstinence, and was not different at 4 or at 6 to 12 weeks of abstinence. In smokers, beta(2)*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar beta(2)*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan.

Conclusions: These data suggest that higher beta(2)*-nAChR availability persists up to 1 month of abstinence and normalizes to nonsmoker levels by 6 to 12 weeks of abstinence from tobacco smoking. These marked and persistent changes in beta(2)*-nAChR availability may contribute to difficulties with tobacco cessation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Azetidines
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Brain Mapping
  • Dominance, Cerebral / physiology
  • Female
  • Follow-Up Studies
  • Humans
  • Image Processing, Computer-Assisted*
  • Iodine Radioisotopes
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Nicotine / adverse effects
  • Receptors, Nicotinic / physiology*
  • Smoking / physiopathology*
  • Smoking Cessation / psychology*
  • Substance Withdrawal Syndrome / diagnostic imaging
  • Substance Withdrawal Syndrome / physiopathology
  • Tobacco Use Disorder / diagnostic imaging*
  • Tobacco Use Disorder / physiopathology
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • A 85380
  • Azetidines
  • Iodine Radioisotopes
  • Receptors, Nicotinic
  • nicotinic receptor beta2
  • Nicotine