WIN 55,212-2-induced reduction of cocaine hyperlocomotion: possible inhibition of 5-HT(3) 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-HT(3) receptor function.
Przegaliński
Edmund
E
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland. przegal@if-pan.krakow.pl
Göthert
Manfred
M
Frankowska
Małgorzata
M
Filip
Małgorzata
M
D000818:Animals; D048588:Benzoxazines; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D000077285:Rimonabant; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology
D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017294:Ondansetron; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003042:Cocaine; D000077285:Rimonabant