Modulation of seizure susceptibility in the mouse by the strychnine‐insensitive glycine recognition site of the NMDA receptor/ion channel complex
Open Access
- 1 February 1990
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 99 (2), 285-288
- https://doi.org/10.1111/j.1476-5381.1990.tb14695.x
Abstract
1 In order to determine whether the strychnine-insensitive glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptor/ion channel complex is fully activated in vivo, the ability of the selective glycine receptor agonist, d-serine, to modulate seizure susceptibility in the mouse has been examined. 2 d-Serine (10–200 μg per mouse, i.c.v.) dose-dependently increased the potency of NMDLA in inducing seizures in Swiss Webster mice by approximately 3 fold. l-Serine was without significant effect. 3 The potency of pentylenetetrazol in inducing seizures was also enhanced by d-, but not l-serine, although the magnitude of the shift (1.6 fold) was considerably less than for NMDLA. 4 Similar doses of d-serine were also able to block the anticonvulsant effect of the non-selective glycine receptor antagonist, kynurenic acid, against seizures induced by NMDLA, but were without effect on the anticonvulsant effect of the competitive NMDA receptor antagonist, 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). 5 d-Serine completely antagonized the protective effect of the selective glycine receptor antagonist, 7-chlorokynurenic acid, against sound-induced seizures in DBA/2 mice, but was less effective in this model against the less selective antagonist, kynurenic acid. 6 The results indicate that in vivo, NMDA receptors are not maximally potentiated by endogenous glycine and suggest an important involvement of the glycine modulatory site on the NMDA receptor/ion channel complex in the pathophysiology of epilepsy.This publication has 21 references indexed in Scilit:
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