Effects of 5-HT3 receptor antagonists on neuroleptic-induced catalepsy in mice.
Typical neuroleptics (e.g. haloperidol) can induce a cataleptic state in rodents by means of striatal DA receptor blockade. It has been shown that drugs which influence central serotonergic (5-HTergic) mechanisms can modify neuroleptic-induced catalepsy, suggesting that dopaminergic transmission is under 5-HTergic modulation. The aim of this study was to examine the effects of bemesetron and granisetron, two selective 5-HT3 receptor antagonists, on this catalepsy in mice. Catalepsy was induced with haloperidol (1.5 mg/kg, i.p.) and measured at 30-min intervals by means of a bar test. Drugs (or saline, for the controls) were 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 to 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 play a role in neuroleptic-induced catalepsy. Considering the high affinities of both antagonists for 5-HT3 receptors, it is tempting to speculate that the potentiation of catalepsy by high doses of them is due to non 5-HT3 receptor mechanisms.
Silva
S R
SR
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, ES, Brazil.
Futuro-Neto
H A
HA
Pires
J G
JG
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced*; D017829:Granisetron / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D051379:Mice; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology
D017829:Granisetron; D006220:Haloperidol; D012702:Serotonin Antagonists; D014326:Tropanes; C042253:bemesetron