N-methyl-D-asparate receptor antagonists abolish the maintenance phase of self-sustaining status epilepticus in rat

We examined the effects of blockers of N-methyl-D-asparate (NMDA) and +/- -alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors on the maintenance of self-sustaining status epilepticus (SSSE) induced in rats by brief intermittent electrical stimulation of the perforant path (PPS). Blocking of NMDA receptor at the PCP site by MK-801 (0.5 mg/kg, i.p.) or ketamine (10 mg/kg, i.p.) as well as at the glycine allosteric site by intrahippocampal 5,7-dichlorokynurenic acid (5,7-DCK, 10 nmol), rapidly and irreversibly aborted both behavioral and electrographic manifestation of SSS. Intrahippocampal injection of the AMPA/kainate receptor blocker 6-cyano7-nitroquinixaline-3-dione (CNQX, 10 nmol) transiently suppressed seizures, which reappeared 4-5 h later. We suggest that the maintenance phase of SSSE depends on activation of NMDA receptors and that NMDA receptor blockers may be a promising class of compounds for the treatment of status epilepticus.