Genetic liability increases propensity to prime-induced reinstatement of conditioned place preference in mice exposed to low cocaine

Abstract

Relapse to drug use after periods of forced or self-imposed abstinence is a central problem in the treatment of addiction; therefore, identification of factors modulating the risk to relapse is a relevant goal of preclinical research. These experiments evaluated the influence of the amount of drug experienced, the duration of drug withdrawal, and individual liability on the propensity to cocaine-induced reinstatement of conditioned place preference (CPP). Mice from the inbred strains C57BL/6J and DBA/2J were trained for CPP with a high (20 mg/kg) or low (5 mg/kg) effective dose of cocaine. After CPP testing, all groups underwent extinction. Twenty-four hours after the extinction test, mice were challenged with saline, a cocaine dose unable to induce CPP (2.5 mg/kg) or an intermediate effective dose (10 mg/kg), and tested for CPP reinstatement. Additional groups of mice trained with the low cocaine dose were left undisturbed for 8 days after extinction test (long withdrawal), retested for extinction, and evaluated for prime-induced reinstatement (0, 2.5, 10 mg/kg of cocaine). Mice trained with the high cocaine dose, but not with the low one, showed prime-induced reinstatement 24 h after the extinction test; DBA/2J mice trained with the low dose showed reinstatement after long withdrawal. These results indicate that reinstatement of CPP by cocaine prime depends on the amount of drug experienced and on an interaction between individual liability and duration of drug abstinence and suggest that the risk to relapse into drug seeking is not prevented by moderated drug consumption.