Conditioned stimulus-induced reinstatement of extinguished cocaine seeking in C57BL/6 mice: a mouse model of drug relapse.

The scarcity of mouse models for relapse to cocaine seeking has curtailed the study of genetic factors that may contribute to susceptibility for drug relapse. To contribute to the development of a new mouse model of drug relapse, C57BL/6 (B6) mice were trained to press a lever for infusions of cocaine (0.35 mg/kg, i.v.) on a fixed ratio 1 schedule of reinforcement during daily 2-h sessions. A light+tone stimulus complex was presented simultaneously with each cocaine infusion. Mice then underwent a series of extinction sessions during which lever presses had no scheduled consequences. As a result, lever pressing gradually declined. In experiment 1, the ability of the cocaine-paired light+tone stimulus complex to reinstate extinguished cocaine-seeking behavior (i.e. non-reinforced responses) was assessed. In experiment 2, the ability of cocaine priming (0, 1, 2.5, 5, 10, 20, and 40 mg/kg, i.p.) to reinstate cocaine-seeking behavior was measured. B6 mice failed to reinstate in response to i.p. cocaine priming; however, they exhibited robust conditioned stimulus-induced reinstatement. These findings suggest that conditioned stimulus-induced reinstatement in B6 mice is a promising model to study genetic and neurobiological factors that alter the ability of cocaine-paired stimuli to elicit relapse to cocaine seeking behavior.