7-Chlorokynurenic acid, a strychnine-insensitive glycine receptor antagonist, inhibits limbic seizure kindling

Abstract

Electrical kindling of the rat amygdala was performed following daily intra-amygdaloid injections of the strychnine-insensitive glycine receptor antagonist 7-chlorokynurenic acid (7-CIKYN) (10 nmol), 7-CIKYN (10 nmol) plus glycine (40 nmol), or vehicle alone. Control (vehicle-treated) animals showed their first fully kindled (Stage 5) seizure after 9.5 +/- 0.8 daily stimulations. Animals pretreated with 7-CIKYN (10 nmol) showed a significant retardation of development of both the electroencephalographic and motor (17.7 +/- 2.9 daily stimulations) components of the seizure response. This inhibitory influence of 7-CIKYN was blocked when glycine (40 nmol) was co-injected daily with the antagonist. The mean initial afterdischarge threshold (ADT) was unaffected by pretreatment with 7-CIKYN (10 nmol). These results provide the first demonstration of an antiepileptogenic action of a strychnine-insensitive glycine receptor antagonist. They further support a key involvement of NMDA receptors in generative mechanisms of epilepsy.