[Serotonergic mechanisms in hippocampal kindled seizures--inhibitory effects of L-5-hydroxytryptophan and 8-hydroxy-2-(di-n-propylamino)tetralin]

Abstract

Serotonin (5-HT) has been considered to possess an inhibitory action against the kindling development, but the role of 5-HT in kindled seizures is unclear. Furthermore, most previous studies have dealt with amygdaloid kindling. To clarify the role of the 5-HT system in epilepsy, we examined the effects of 5-hydroxytryptophan (5-HTP), a precursor which elevates brain 5-HT, and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT 1 a receptor agonist, on seizures kindled from the feline hippocampus (HIP). Following the completion of HIP kindling, five cats received 0.9% saline, 5-HTP (20 or 40 mg/kg, i.p.) or 8-OH-DPAT (0.1 or 1.0 mg/kg, i.v.). Drugs were administered 15 min (8-OH-DPAT) or 1 hr (5-HTP) prior to electrical stimulation at the generalized seizure triggering threshold, and the anticonvulsant effects were assessed by the behavioral seizure stage and afterdischarge (AD) duration. Both 5-HTP and 8-OH-DPAT suppressed dose-dependently HIP-kindled seizures. The administration of 5-HTP at 40 mg/kg and of 8-OH-DPAT at 1.0 mg/kg produced a marked or complete suppression of HIP-kindled seizures in most of the cats tested, and was found to significantly reduce the seizure stage when compared with the saline control. Both drugs tended to shorten the AD duration, but this effect did not reach statistically significant levels. The present data suggest that the 5-HT system plays an important role in HIP-kindled seizures, and that the 5-HT 1 a receptors have an inhibitory effect on the kindled focal epileptic activity of the HIP.