Serotonin2C receptors (5-HT2C R) control expression of cocaine-induced conditioned hyperactivity

Environmental cues can become classically conditioned to cocaine exposure and are known to contribute to drug craving and relapse in addicts. The 5-HT2C receptor (5-HT2C R) has been shown to control the behavioral effects of acute cocaine administration and, in the present study, we investigated the role of this receptor in the expression of cocaine-induced conditioned hyperactivity. Rats received repeated pairings of a distinct test environment with either saline or cocaine (15 mg/kg, i.p.) for 7 days. In a drug-free test 2 days after the last pairing, expression of conditioned hyperactivity was seen in the rats previously exposed to cocaine in the test environment. The 5-HT2C R agonist MK 212 (0.0625-0.5 mg/kg, i.p., 5 min before test) significantly decreased, while the 5-HT2C R antagonist SB 242084 (0.5-1 mg/kg, i.p. 30 min prior to test) enhanced, expression of cocaine-induced conditioned hyperactivity. The effective doses of MK 212 and SB 242084 did not alter basal activity on the test session. These results suggest that the 5-HT2C R controls expression of cocaine-induced conditioned hyperactivity and suggest that such ligands may be useful in preventing relapse and promoting abstinence in cocaine-dependent individuals.