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 various 5-HT receptor antagonists on hippocampal partial seizures generated by low-frequency electrical stimulation in male Wistar rats. The seizure threshold and severity were determined by measuring the pulse number threshold and primary and secondary afterdischarges, respectively, and the latency of secondary discharge was also determined. The administration of either the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-c yclohe xanecarboximimde 3 HCl (WAY 100635, 0.1-1 mg/kg i.p.), the selective 5-HT(3) receptor antagonist granisetron (0.3-3 mg/kg i.p.), the selective 5-HT(2A) receptor antagonist R-(+)-a-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidine-methanol (MDL 100907, 0.3-3 mg/kg i.p.) or the 5-HT(2B,C) receptor antagonist antagonist N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea HCl (SKB 200646A, 5-50 mg/kg i.p.) did not alter the pulse number threshold compared to vehicle-treated animals. However, the acute administration of WAY 100635 (0.3 mg/kg) and M100907 (1 mg/kg) significantly increased, whereas granisetron (1 mg/kg) decreased, the primary afterdischarge duration compared to vehicle-treated animals. The latency of secondary after discharge was significantly decreased by WAY 100635 (1 mg/kg) and granisetron (3 mg/kg) compared to vehicle-treated animals. These results suggest that in this model, the antagonism of 5-HT(1A), 5-HT(2A), 5-HT(3) or 5-HT(2B,C) receptors do not lower or raise seizure threshold. However, the antagonism of 5-HT(1A) receptors may increase or augment seizure severity.
Watanabe
K
K
Department of Neuropsychiatry, Faculty of Medicine, University of Tokyo, 113-8655, Tokyo, Japan.
Ashby
C R
CR
Katsumori
H
H
Minabe
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005464:Fluorobenzenes / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008124:Locomotion; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012720:Severity of Illness Index; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D005464:Fluorobenzenes; D017829:Granisetron; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014508:Urea; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C079049:volinanserin