Over the past three decades there has been a strong focus in the field of addiction towards the development of vaccines for the prevention and treatment of tobacco smoking (nicotine dependence). Based on preclinical studies in rodents, the presumed mechanism of action is that the antibodies produced by vaccination, bind to nicotine and decrease the rate and the amount of nicotine that is able to cross the blood brain barrier and occupy nicotinic acetylcholine receptors (nAChR) in the mesocorticolimbic reward pathway. In the present study, we propose to validate this mechanism in living human smokers. Specifically, we will image brain 22 nAChR using the nicotinic agonist [123I]5 IA 85380 ([123I]5 IA) and single photon emission computed tomography (SPECT) to determine the amount of nicotine occupancy of brain 22 nAChR after an IV nicotine challenge in smokers before and after vaccination with the NicVax vaccine. We hypothesize that after vaccination, the amount of nicotine occupying 22 nAChR will be reduced by at least 50%. If confirmed, this reduction in the amount of nicotine occupying nAChR will explain why, vaccinated individuals will be less likely to become addicted if they smoke, and current smokers will not experience the same satisfaction from smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA024388-02
Application #
7626480
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Kautz, Mary A
Project Start
2008-06-01
Project End
2011-07-31
Budget Start
2010-02-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$223,256
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Esterlis, Irina; Hannestad, Jonas O; Perkins, Evgenia et al. (2013) Effect of a nicotine vaccine on nicotine binding to ?2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers. Am J Psychiatry 170:399-407
Cosgrove, Kelly P; Krantzler, Erica; Frohlich, Erin B et al. (2009) Dopamine and serotonin transporter availability during acute alcohol withdrawal: effects of comorbid tobacco smoking. Neuropsychopharmacology 34:2218-26