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-HT(2A) receptor antagonist) or SDZ SER-082 (a 5-HT(2C) 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 mg/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-HT(2A) and 5-HT(2C) receptors are not significant to cocaine rewarding effects. However, they show the importance of the 5-HT(2A) receptors (but not 5-HT(2C) receptors) in cocaine-priming- and cue-provoked reinstatement. Since drugs that reduce cocaine seeking also alleviate cocaine craving, 5-HT(2A) receptor antagonists may be considered to be of possible clinical application for the treatment of cocaine dependence.
Filip
Małgorzata
M
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. filip@if-pan.krakow.pl
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D005464:Fluorobenzenes / Q000494:pharmacology*; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D012646:Self Administration; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*
D005464:Fluorobenzenes; D010636:Phenols; D044348:Receptors, Serotonin, 5-HT2; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; C076033:SR 46349B; D003042:Cocaine