Postsynaptic 5-HT1B receptors modulate electroshock-induced generalised seizures in rats.

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.

• 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)

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

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)