The effect of the non-NMDA receptor antagonists GYKI 52466 and NBQX and the competitive NMDA receptor antagonist d-CPPene on the development of amygdala kindling and on amygdala-kindled seizures

Abstract

A competitive (NBQX) and a non-competitive (GYKI 52466) AMPA antagonist and a competitive NMDA antagonist ( d-CPPene) were tested against the development of kindling and against fully kindled seizures in amygdalakindled rats. GYKI 52466, 10 mg/kg given i.p. 5 min prior to electrical stimulation in fully kindled animals, reduces both the cortical after-discharge duration and the behavioural seizure score. GYKI 52466, 20 mg/kg, reduces seizure score and after-discharge duration significantly (after 5–30 min) but the animals show severe motor side effects and an irregular cortical and hippocampal EEG. Administration of GYKI 52466, 10 mg/kg, prior to kindling stimulation on days 3–8, does not slow the development of kindling. NBQX, 20 mg/kg or 40 mg/kg i.p., 30 min prior to stimulation, significantly reduces the seizure score in fully kindled animals. NBQX 20 mg/kg i.p. has no effect on the development of kindling. d-CPPene, 8 mg/kg or 12 mg/kg, 120 min prior to stimulation reduces the behavioural seizure score in fully kindled animals. d-CPPene, 8 mg/kg on days 3–8, delays the development of kindling. NMDA receptors play a key role in the kindling process. Expression of kindled seizures involves non-NMDA and NMDA receptors.