WIN 55,212-2-induced reduction of cocaine hyperlocomotion: Possible inhibition of 5-HT3 receptor function

We examined the effect of WIN 55,212-2 (an agonist of cannabinoid receptors) and its enantiomer WIN 55,212-3, as well as of ondansetron (an antagonist of serotonin (5-HT)3 receptors) on the cocaine-induced locomotor hyperactivity in rats. WIN 55,212-2, but not WIN 55,212-3, in doses of 3 and 6 mg/kg which did not affect the basal locomotor activity, dose-dependently reduced the hyperactivation evoked by cocaine. The inhibitory effect of WIN 55,212-2 was not affected by rimonabant (an antagonist of cannabinoid receptors). Like in the case of WIN 55,212-2, the cocaine-induced hyperlocomotion was reduced in a dose-dependent manner by ondansetron (0.03-0.3 mg/kg). The obtained results indicate that the inhibitory effect of WIN 55,212-2 on cocaine hyperactivation is stereoselective and is not mediated by cannabinoid receptors. Moreover, together with the literature data they may suggest that this effect of WIN 55,212-2 involves inhibition of the 5-HT3 receptor function.