Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking behavior in rats

Previous studies have indicated a role of serotonin (5-HT)(2) receptors in modulation of the behavioral effects of cocaine. In the present study, the efficacy of SR 46349B (a 5-HT2A receptor antagonist) or SDZ SER-082 (a 5-HT2C receptor antagonist) in altering cocaine seeking behavior was examined in rats. Rats were trained to press a lever for cocaine (0.5 mg/kg/infusion, iv) paired with the cue (light + tone). After stabilization of self-administration response, the animals underwent daily extinction sessions during which responding had no consequences. The cocaine seeking behavior was reinstated by cocaine priming (10 mg/kg, ip) or by presentation of the cue. Neither SR 46349B (0.25-1 nig/kg) nor SDZ SER-082 (0.25-1 mg/kg) altered the maintenance of cocaine self-administration. SR 46349B (0.5-1 mg/kg) decreased responding to the cocaine priming dose and reduced cue-induced reinstatement, while SDZ SER-082 failed to alter both cue- and cocaine priming-induced reinstatement. These findings indicate that 5-HT2A and 5-HT2C receptors are not significant to cocaine rewarding effects. However, they show the importance of 5-HT2A receptors (but not 5-HT2C receptors) in cocaine-priming- and cue-provoked reinstatement. Since drugs that reduce cocaine seeking also alleviate cocaine craving, 5-HT2A receptor antagonists may be considered to be of possible clinical application for the treatment of cocaine dependence.