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Neuropharmacology of nicotine relapse

Institution: Cedars-Sinai Medical Center
Investigator(s): Xiu Liu, M.D., Ph.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12KT-0188 Award: $149,175
Subject Area: Nicotine Dependence
Award Type: New Investigator Awards

Initial Award Abstract
Tobacco smoking is the most important preventable cause of death in the United States. Nearly 25% of the U.S. population smokes and each year more than 425,000 Americans die of tobacco-related illnesses. A formidable challenge for the treatment of nicotine addiction is the highly vulnerability to relapse following abstinence, which is one of the principal characteristics of tobacco smoking. Many smokers want to quit, but only approximately 3% of smokers successfully remain abstinence each year, which is less than 10% of those who attempt to quit. One of the major issues involved in relapse is that various factors that are linked to smoking (e.g. smell of cigarette smoke, finishing a meal at a restaurant, drinking, etc.) can trigger memories of smoking and it’s pleasurable components both consciously and subconsciously. These factors are called cues. The proposed experiments will develop an animal model to study the influence of cues on nicotine relapse after abstinence. Rats are trained operantly to self-administer nicotine and to associate a light cue with infusion of nicotine. Then, the operant (lever press) responses are extinguished by withholding nicotine and its associated light cue. After extinction, the rats are tested to determine the ability of the light cue to reinstate lever responding in the absence of the nicotine infusion. The first experiment will test the ability of the light cue to reinstate lever pressing 1, 2, 3, 4, 5 weeks and 2 months after training in order to determine how long the cue effect lasts. The next experiment will compare the ability of the light cue to reinstate lever pressing with that of nicotine priming. The third experiment will use drugs to study what chemicals in the brain are involved in the cue-induced relapse. Drugs to be tested include compounds that have been used to treat nicotine addiction. The results obtained from the proposed experiments might have important clinical implications for developing strategies for the treatment and prevention of relapse.