5-HT2 RECEPTOR BLOCKADE BY ICI-170,809 DOES NOT AFFECT THE INHIBITORYEFFECT OF THE 5-HT1A RECEPTOR-LIGAND GEPIRONE ON NEUROLEPTIC-INDUCED CATALEPSY

Considerable experimental evidence suggests that central dopaminergic (DA) transmission is under serotonergic (5-HTergic) modulation. For in stance, neuroleptic-induced catalepsy (NTC) in rodents, a behavior mai nly due to blockade of DA receptors in the striatum, can be affected b y 5-HTergic manipulation It has been shown that ligands of 5-HT1A rece ptors (e.g. buspirone, gepirone) reduce NIC, while 5-HT2 receptor anta gonists (e.g. ritanserin) do not affect this phenomenon. However, the role of 5-HT2 receptors in the modulation of NIC is still controversia l and there is evidence from behavioral models other than NIC suggesti ng the existence of functional interaction between the two subtypes of 5-HT receptors. The present study was designed to evaluate the effect of ICI 170,809 (a selective 5-HT2 receptor antagonist) on NIC and to test the possible effect of this drug on the anticataleptic effect of gepirone (GP). Male Wistar rats weighing 300-350 g were used, and each animal (7 per group, 4 groups) was used only once. Catalepsy was indu ced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Animals received either ICI 170,809 (3 mg/kg, ip) or 0.9% saline (SL; 0.8 ml, ip) 30 min before H. At 110 min after H, the rats received GP (1 mg/kg, ip) or SL, (0.8 ml, ip). GP signifi cantly attenuated NIC (e.g. 739 +/- 106 s vs 1009 +/- 85 s for control s, at 150 min after H), while ICI 170,809 did not significantly affect the phenomenon (e.g. 978 +/- 89 s vs 1009 +/- 85 s for controls, at 1 50 min after H). Pretreatment with ICI 170,809 did not significantly m odify the anticataleptic effect of GP (e.g. 617 +/- 90 s vs 739 +/- 10 6 s for SL-pretreated animals, at 150 min after H). These results conf irm reports of the anticataleptic effect of GP and the lack of effect of 5-HT2 receptor antagonists on NIC. Moreover, these data also sugges t the absence of functional interactions between central 5-HT1A and 5- HT2 receptors in this model of DA transmission.