EFFECTS OF THE 5-HT RECEPTOR ANTAGONISTS CYANOPINDOLOL, ICI 169,369, CISAPRIDE AND GRANISETRON ON NEUROLEPTIC-INDUCED CATALEPSY IN MICE

Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodent s. Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduc e neuroleptic-induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays a role in the modulation of nigrostriatal do paminergic transmission. The present study was designed to evaluate th e participation of other 5-HT receptor subtypes in NIC. Adult albino m ice (both sexes, 26-35 g) were used. Catalepsy was induced with halope ridol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2 receptor antagonist) and granisetron (a 5-HT3 receptor ant agonist) were used. Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and clomipramine, a 5-HT neuronal uptake blocker , were also employed. These drugs were injected ip, 20 min before H, w ith each animal (9-10 per group) used only once. Cyanopindolol (0.3 mg /kg) or ICI 169,369 (5 mg/kg) did not significantly affect NIC (375 +/ - 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h after H). B uspirone (1 mg/kg) reduced, while pretreatments with either granisetro n (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg) potentiat ed the cataleptic effect of H (107 +/- 19,576 +/- 52, 815 +/- 76 and 8 00 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H). The se data suggest that central 5-HT3 receptors, in addition to 5-HT1A re ceptors, play a role in NIC, whereas 5-HT1B, 5-HT1C and 5-HT2 receptor s seem not to be involved in this phenomenon.