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Kelly P. Cosgrove, PhD; Jeffery Batis, PhD; Frederic Bois, PhD; Paul K. Maciejewski, PhD; Irina Esterlis, PhD; Tracy Kloczynski, MA; Stephanie Stiklus, BA; Suchitra Krishnan-Sarin, PhD; Stephanie O’Malley, PhD; Edward Perry, MD; Gilles Tamagnan, PhD; John P. Seibyl, MD; Julie K. Staley, PhD

Arch Gen Psychiatry. 2009;66(6):666-676.

Context  Available levels of nicotinic acetylcholine receptors containing the β₂ subunit (β₂*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in β₂*-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 β₂*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in β₂*-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 ([¹²³I]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 [¹²³I]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 [¹²³I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest.

Results  Compared with nonsmokers, β₂*-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, β₂*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar β₂*-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 β₂*-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 β₂*-nAChR availability may contribute to difficulties with tobacco cessation.

Author Affiliations: Department of Psychiatry, Yale University School of Medicine (Drs Cosgrove, Batis, Bois, Maciejewski, Esterlis, Krishnan-Sarin, O’Malley, Perry, and Staley and Mss Kloczynski and Stiklus), Department of Psychiatry, Veterans Affairs Connecticut Healthcare System (Drs Cosgrove, Batis, Bois, Esterlis, Perry, and Staley and Mss Kloczynski and Stiklus), and Institute for Neurodegenerative Disorders (Drs Tamagnan and Seibyl), West Haven, Connecticut.

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