Abstract |
1. Although an important regulatory role for serotonin (5-HT) in seizure activation and propagation is well established, relatively little is known of the function of specific 5-HT receptor subtypes on seizure modulation. 2. The aim of the present study was to investigate the role of 5-HT(1A, 1B and 1D) receptors in modulating generalised seizures in the rat maximal electroshock seizure threshold (MEST) test. 3. The mixed 5-HT receptor agonists SKF 99101 (5-20 mg kg(-1) i.p.) and RU 24969 (1-5 mg kg(-1) i.p.), 0.5 h pretest, both produced marked dose-related increases in seizure threshold. These agents share high affinity for 5-HT(1A, 1B and 1D) receptors. 4. Antiseizure effects induced by submaximal doses of these agonists were maintained following p-chlorophenylalanine (150 mg kg(-1) i.p. x 3 days)-induced 5-HT depletion. 5. The anticonvulsant action of both SKF 99101 (15 mg kg(-1) i.p.) and RU 24969 (2.5 mg kg(-1) i.p.) was dose-dependently abolished by the selective 5-HT1B receptor antagonist SB-224289 (0.1-3 mg kg(-1) p.o., 3 h pretest) but was unaffected by the selective 5-HT1A receptor antagonist WAY 100635 (0.01-0.3 mg kg(-1) s.c., 1 h pretest). This indicates that 5-HT1B receptors are primarily involved in mediating the anticonvulsant properties of these agents. 6. In addition, the ability of the 5-HT(1B/1D) receptor antagonist GR 127935 (0.3-3 mg kg(-1) s.c., 60 min pretest) to dose-dependently inhibit SKF 99101-induced elevation of seizure threshold also suggests possible downstream involvement of 5-HT1D receptors in the action of this agonist, although confirmation awaits the identification of a selective 5-HT1D receptor antagonist. 7. Overall, these data demonstrate that stimulation of postsynaptic 5-HT1B receptors inhibits electroshock-induced seizure spread in rats.
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Authors | Tania O Stean, Alan R Atkins, Christian A Heidbreder, Leann P Quinn, Brenda K Trail, Neil Upton |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 144
Issue 5
Pg. 628-35
(Mar 2005)
ISSN: 0007-1188 [Print] England |
PMID | 15678098
(Publication Type: Journal Article)
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Chemical References |
- Indoles
- Piperidones
- Receptor, Serotonin, 5-HT1B
- Receptor, Serotonin, 5-HT1D
- SB 22489G
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin Antagonists
- Serotonin Receptor Agonists
- Spiro Compounds
- Receptor, Serotonin, 5-HT1A
- SKF 99101H
- 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
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Topics |
- Animals
- Electroshock
- Indoles
(pharmacology)
- Male
- Piperidones
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT1A
(drug effects)
- Receptor, Serotonin, 5-HT1B
(drug effects)
- Receptor, Serotonin, 5-HT1D
(drug effects)
- Seizures
(drug therapy)
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin Antagonists
(pharmacology)
- Serotonin Receptor Agonists
(pharmacology)
- Spiro Compounds
(pharmacology)
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