Stimulation of 5-HT(1A) receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

1. We studied whether the stimulation of 5-HT(1A) receptors by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a specific 5-HT(1A) receptor agonist, reduced electroencephalographic (EEG) seizures induced by intrahippocampal injection of 0.04 μg in 0.5 μl of the glutamate analogue kainic acid in freely-moving rats. 2. Pretreatment with 8-OH-DPAT 15 min earlier at the same site as kainic acid injection, caused a dose-dependent decrease of kainic acid-induced seizure activity. One and 10 μg significantly reduced the total time spent in seizures by 72% on average and the total number of seizures by 58% (P <0.01) and 43% (P <0.05) respectively. The latency to onset of the first seizure was increased 2.8 times (P <0.01) only after 1 μg 8-OH-DPAT; 0.1 μg was ineffective on all seizure parameters. 3. Systemic administration of 25, 100 and 1000 μg kg^-1 8-OH-DPAT significantly reduced the total number of seizures and the total time in seizures induced by intrahippocampal kainic acid by 52% and 74% on average. The latency to onset of the first seizure was delayed 1.8 times by 100 and 1000 μg kg^-1 (P <0.05). 4. The anticonvulsant action of 8-OH-DPAT given intrahippocampally or systemically was significantly blocked by 5 μg, but not 1 μg WAY 100635, a selective 5-HT(1A) receptor antagonist, administered in the hippocampus before the agonist. 5. These results indicate that postsynaptic 5-HT(1A) receptors in the hippocampus mediate the anticonvulsant action of 8-OH-DPAT and that their stimulation has an inhibitory role in the generation of limbic seizures.