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Stimulation of 5‐HT 1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats
Author(s) -
Gariboldi Marco,
Tutka Piotr,
Samanin Rosario,
Vezzani Annamaria
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15745.x
Subject(s) - kainic acid , medicine , agonist , endocrinology , anticonvulsant , stimulation , 8 oh dpat , hippocampus , 5 ht1a receptor , chemistry , epilepsy , receptor , 5 ht receptor , serotonin , anesthesia , glutamate receptor , neuroscience , biology
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.