Effect of acute administration of various 5-HT receptor agonists on focal hippocampal seizures in freely moving rats

Abstract

In this study, we assessed the effects of the acute administration of various 5-HT receptor agonists 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 and the latency of secondary discharge was also determined. The administration (0.1-1 mg/kg, i.p.) of either the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-aminopropyl)tetralin (8-OH-DPAT), or the selective 5-HT3 receptor agonist, 4-amino-(6-chloro-2-pyridyl)-1-piperidine (SR 57227A, 0.3-3 mg/kg, i.p.), did not alter any of the seizure parameters compared to those in vehicle-treated animals. Similarly, the administration of 0.3 and 1 mg/kg, i.p., of the 5-HT2A,C receptor agonist, (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), did not alter any of the seizure parameters, whereas 3 mg/kg significantly decreased the latency of the secondary afterdischarge compared to that in vehicle-treated animals. The selective serotonin reuptake inhibitor, (+/-)-fluoxetine (2 mg/kg, i.p.), significantly increased the pulse number threshold and decreased the primary afterdischarge duration compared to those in vehicle-treated animals. In contrast, higher doses (6 or 20 mg/kg, i.p.) of fluoxetine did not significantly alter any of the seizure parameters measured. These results suggest that, in this model, stimulation of 5-HT1A, 5-HT2A,C and 5-HT3 receptors does not alter seizure threshold or severity and that the blockade of 5-HT uptake produced by a low dose of fluoxetine appears to increase seizure threshold and decrease seizure severity.