Failure of ondansetron to block the discriminative or reinforcing stimulus effects of cocaine in the rat

Ondansetron (GR38032F), a serotonin 5HT₃ antagonist, is active in numerous behavioral paradigms and neurochemical systems. Since 5HT₃ antagonists have been suggested as therapeutic agents for the treatment of drug abuse, the action of ondansetron on cocaine drug discrimination and self-administration paradigms in rats was investigated. Doses of ondansetron (0.001-1.0 mg/kg) had no effect on the discriminative stimulus properties of 10 mg/kg cocaine. In contrast, SCH23390, a dopamine D₁ antagonist known to block cocaine discrimination, acted as previously reported. Ondansetron did not augment the effects of SCH23390, but at higher doses, combinations of ondansetron and SCH23390 produced disruption of lever pressing in the presence of cocaine. Ondansetron (0.001-1.0 mg/kg) had no effect on the self-administration of various doses of cocaine, nor did it have any effect on reacquisition of cocaine self-administration in animals with a history of active administration followed by a period of abstinence. As before, SCH23390, known to block cocaine self-administration, acted as previously reported. Although other 5HT antagonists may prove to be efficacious in cocaine abuse, ondansetron appears unlikely to alter the subjective or rewarding stimulus properties of cocaine.