The effect of the acute administration of various selective 5-HT receptor antagonists on focal hippocampal seizures in freely-moving rats

In this study, we assessed the effects of the acute administration of vario us 5-HT receptor antagonists on hippocampal partial seizures generated by l ow-frequency electrical stimulation in male Wistar rats. The seizure thresh old and severity were determined by measuring the pulse number threshold an d primary and secondary afterdischarges, respectively, and the latency of s econdary discharge was also determined. The administration of either the se lective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl ]ethyl]-N-(pyridinyl)-cyclohexanecarboximimde 3 HCl (WAY 100635, 0.1-1 mg/k g i.p.), the selective 5-HT3 receptor antagonist granisetron (0.3-3 mg/kg i .p.), the selective 5-HT2A receptor antagonist R-(+)-a-(2,3-dimethoxyphenyl )-1-[2-(4-fluorophenyl)ethyl]-4-piperidine-methanol (MDL 100907, 0.3-3 mg/k g i.p.) or the 5-HT2B,C receptor antagonist antagonist N-(1-methyl-5-indoly l)-N'-(3-pyridyl) urea HCl (SKB 100646A, 5-50 mg/kg i.p.) did not alter the pulse number threshold compared to vehicle-treated animals. However, the a cute administration of WAY 100635 (0.3 mg/kg) and M100907 (1 mg/kg) signifi cantly increased, whereas granisetron (1 mg/kg) decreased. the primary afte rdischarge duration compared to vehicle-treated animals. The latency of sec ondary after discharge was significantly decreased by WAY 100635 (1 mg/kg) and granisetron (3 mg/kg) compared to vehicle-treated animals. These result s suggest that in this model, the antagonism of 5-HT1A, 5-HT2A, 5-HT3 or 5- HT2B,C receptors do not lower or raise seizure threshold. However, the anta gonism of 5-HT1A receptors may increase or augment seizure severity. (C) 20 00 Elsevier Science B.V. All rights reserved.