Characterization of Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Smoking Relapse: Use of Animal Models

The behavioral motivation effects of nicotine-conditioned stimuli (cues) have been systematically examined in our laboratory using animal models of smoking relapse. Rats were trained to press a lever for intravenous self-administration of nicotine. To establish a nicotine-conditioned cue, an auditory/visual stimulus was associated with each nicotine infusion. Then, lever-responding was extinguished and after extinction reinstatement tests were conducted in which the cue was response-contingently re-presented without nicotine delivery. The reinstated responses on the previously nicotine-reinforced lever were indicative of relapse to nicotine-seeking behavior. The animal model has shown good validity as a simulation of human smoking and relapse after abstinence. This chapter presents an overview of the testing procedures and characterization of conditioned behavior-motivating effects of nicotine cue, including interaction of the nicotine cue with stress challenge and nicotine priming to reinstate nicotine seeking. An array of pharmacological substrates has been found to be responsible for the cue effect. These preclinical studies could shed light on the behavioral and neurobiological mechanisms of smoking relapse.