EFFECT OF ACUTE ADMINISTRATION OF VARIOUS 5-HT RECEPTOR AGONISTS ON FOCAL HIPPOCAMPAL SEIZURES IN FREELY MOVING RATS

In this study, we assessed the effects of the acute administration of various 5-HT receptor agonists on hippocampal partial seizures generat ed by low-frequency electrical stimulation in male Wistar rats. The se izure threshold and severity were determined by measuring the pulse nu mber threshold and primary and secondary afterdischarges and the laten cy 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 a gonist, 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 th ose in vehicle-treated animals. Similarly, the administration of 0.3 a nd 1 mg/kg, i.p., of the 5-HT2A,C receptor agonist, (+/-)-2,5-dimethox y-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 decrea sed the primary afterdischarge duration compared to those in vehicle-t reated animals. In contrast, higher doses (6 or 20 mg/kg, i.p.) of flu oxetine did not significantly alter any of the seizure parameters meas ured. These results suggest that, in this model, stimulation of 5-HT1A , 5-HT2A,C and 5-HT3 receptors does not alter seizure threshold or sev erity and that the blockade of 5-HT uptake produced by a low dose of f luoxetine appears to increase seizure threshold and decrease seizure s everity. (C) 1998 Elsevier Science B.V. All rights reserved.