Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats

To investigate the role of strychnine-insensitive glycine receptors in epilepsy, we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine-insensitive glycine receptor antagonist, on amygdala kindling development and previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or 20 μg) suppressed amygdala kindling development, assessed according to the motor seizure stage and afterdischarge development, in a dose-dependent manner. However, 7-CK had no significant effect on previously kindled seizures at either of these doses nor did 20 μg at any time (15 min, 30 min, 2 h, and 24 h) after injection studied. These results demonstrate that this selective strychnine-insensitive glycine receptor antagonist has antiepileptogenic activity and suggest a role for the glycine receptors in the contribution of the NMDA receptor complex to epileptogenic events.