The International Journal of Neuropsychopharmacology

Research Article

Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler

Irina Esterlisa1 c1, Effie M. Mitsisa4, Jeffery C. Batisa3, Frederic Boisa1, Marina R. Picciottoa1, Stephanie M. Stiklusa1, Tracy Kloczynskia1, Edward Perrya1, John P. Seibyla3, Sherry McKeea1, Julie K. Staleya1a2 and Kelly P. Cosgrovea1

a1 Department of Psychiatry, Yale University School of Medicine and the Veteran's Affairs Connecticut Healthcare System (VACHS), West Haven, USA

a2 Department of Diagnostic Radiology, Yale University School of Medicine and the Veteran's Affairs Connecticut Healthcare System (VACHS), West Haven, USA

a3 Institute for Neurodegenerative Disorders, New Haven, USA

a4 Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA


The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2–5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5–5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.

(Received February 11 2010)

(Reviewed March 14 2010)

(Revised September 03 2010)

(Accepted September 10 2010)

(Online publication October 29 2010)

† Served as joint senior authors for this paper.