Brain beta(2)*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler

作者：Esterlis Irina^*; Mitsis Effie M; Batis Jeffery C; Bois Frederic; Picciotto Marina R; Stiklus Stephanie M; Kloczynski Tracy; Perry Edward; Seibyl John P; McKee Sherry; Staley Julie K; Cosgrove Kelly P

来源：International Journal of Neuropsychopharmacology, 2011, 14(3): 389-398.

DOI：10.1017/S1461145710001227

• beta(2)*-nAChR occupancy
• nicotine
• nicotine inhaler
• SPECT brain imaging

The Nicotrol (R) (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 (beta(2)*-nAChRs). Previous studies examined beta(2)*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of beta(2)*-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 [I-123]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [I-123]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 beta(2)*-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 beta(2)*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.

• 出版日期2011-4