Tobacco Smoking & Nicotinic Acetylcholine Receptors

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DESCRIPTION (provided by applicant): Tobacco smoking is highly addictive and the source of a multitude of social, economic and medical consequences. Tobacco smoking kills more Americans than accidents, alcoholism, fires, illegal drugs, AIDS, murder and suicide combined and is responsible for approximately 400,000 premature deaths per year in the USA. Despite the overwhelming evidence of the medical risks associated with cigarette smoking, approximately 20% of the US population continues to smoke. These devastating costs to society underscore the need for research into the neurochemical mechanisms underlying the development and maintenance of the addiction to cigarette smoking. By understanding the neurochemical substrates promoting the addiction to cigarettes better treatments for this destructive and costly brain disorder may be developed. The nicotinic acetylcholine receptor (nAChR) is the initial site action of nicotine, the primary addictive chemical in tobacco smoke. In the present proposal, we seek to image the agonist binding site on beta2-nicotinic acetylcholine receptor (nAChR) using single photon emission computed tomography (SPECT) and the radiotracer [123115-1A-85830 (5-1A) in tobacco smokers over their first month of abstinence. Specifically, we propose 1) to determine if 5-IA binding to nAChR in brain is elevated in recently abstinent tobacco smokers as compared to age, race and sex-matched nonsmokers; 2) to determine if 5-1A binding to nAChR in smokers normalizes after four weeks of abstinence maintained using contingency management and 3) to determine if 5-1A binding to nAChR in brain correlates with [3H]nicotine binding in polymorphonuclear lymphocytes. These studies will characterize the regulatory state of the agonist binding site on the nicotinic receptor in smokers over the first month of smoking cessation, which will help guide the development of targeted treatment strategies to assist this severely addicted population.