5-HT2 receptor blockade by ICI 170,809 does not affect the inhibitory effect 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 instance, neuroleptic-induced catalepsy (NIC) in rodents, a behavior mainly due to blockade of DA receptors in the striatum, can be affected by 5-HTergic manipulation. It has been shown that ligands of 5-HT1A receptors (e.g. buspirone, gepirone) reduce NIC, while 5-HT2 receptor antagonists (e.g. ritanserin) do not affect this phenomenon. However, the role of 5-HT2 receptors in the modulation of NIC is still controversial and there is evidence from behavioral models other than NIC suggesting 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 induced with haloperidol (H; 1 mg/kg, i.p.) and measured at 30-min intervals by means of a bar test. Animals received either ICI 170,809 (3 mg/kg, i.p.) or 0.9% saline (SL; 0.8 ml, i.p.) 30 min before H. At 110 min after H, the rats received GP (1 mg/kg, i.p.) or SL (0.8 ml, i.p.). GP significantly attenuated NIC (e.g. 739 +/- 106 s vs 1009 +/- 85 s for controls, 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 150 min after H). Pretreatment with ICI 170,809 did not significantly modify the anticataleptic effect of GP (e.g. 617 +/- 90 s vs 739 +/- 106 s for SL-pretreated animals, at 150 min after H). These results confirm reports of the anticataleptic effect of GP and the lack of effect of 5-HT2 receptor antagonists on NIC. Moreover, these data also suggest the absence of functional interactions between central 5-HT1A and 5-HT2 receptors in this model of DA transmission.