EFFECTS OF 5-HT3 RECEPTOR ANTAGONISTS ON NEUROLEPTIC-INDUCED CATALEPSY IN MICE

Typical neuroleptics (e.g. haloperidol) can induce a cataleptic state in rodents bq; means of striatal DA receptor blockade. It has been sho wn that drugs which influence central serotonergic (5-HTergic) mechani sms can modify neuroleptic-induced catalepsy, suggesting that dopamine rgic transmission is under 5-HTergic modulation. The aim of this study was to examine the effects of bemesetron and granisetron, two selecti ve 5-HT3 receptor antagonists, on this catalepsy in mice. Catalepsy wa s induced with haloperidol (1.5 mg/kg, i.p.) and measured at 30-min in tervals by means of a bar test. Drugs (or saline, for the controls) we re injected i.p. 20 min before haloperidol, with each animal used only once. Bemesetron significantly reduced catalepsy at a dose of 1 mg/kg , whilst 10 mg/kg potentiated the phenomenon and 0.1 mg/kg was found t o be without effect. Granisetron inhibited catalepsy at doses of 0.04 and 0.1 mg/kg, while 4 mg/kg of the antagonist significantly increased the duration of catalepsy. These data suggest that 5-HT3 receptors pl ay a role in neuroleptic-induced catalepsy. Considering the high affin ities of both antagonists for 5-HT3 receptors, it is tempting to specu late that the potentiation of catalepsy by high doses of them is due t o non 5-HT3 receptor mechanisms.