Abstract
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.
Original language | English |
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Pages (from-to) | 813-818 |
Number of pages | 6 |
Journal | British Journal of Pharmacology |
Volume | 119 |
Issue number | 5 |
Publication status | Published - 1996 |
Keywords
- 5-HT(1A) receptors
- 8-hydroxy-2-(di-n-propylamino) tetralin
- Anticonvulsants
- EEG
- Hippocampus
- Kainic acid
- Limbic seizures
- WAY 100635
ASJC Scopus subject areas
- Pharmacology