Serotonin_2C receptors (5-HT_2CR) 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-HT_2C receptor (5-HT_2CR) 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-HT_2CR agonist MK 212 (0.0625-0.5 mg/kg, i.p., 5 min before test) significantly decreased, while the 5-HT_2CR 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-HT_2CR 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.