AMYGDALOID KINDLING BY REPEATED FOCAL N-METHYL-D-ASPARTATE ADMINISTRATION - COMPARISON WITH ELECTRICAL KINDLING

Limbic seizures were kindled by repeated, daily intra-amygdaloid microinjections of N-methyl-D-aspartate (NMDA; 2 nmol). The seizures, and accompanying afterdischarges, closely resembled those seen following electrical kindling of the amygdala. As with electrical kindling, co-administration of the competitive NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7; 70 nmol) prevented the development of seizure activity. NMDA-induced kindling was durable, lasting at least 1 month, and showed positive transfer to electrical kindling. Fully kindled seizures were inhibited by co-administration of the potent NMDA receptor antagonist DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) with the agonist. These results strongly support a role for NMDA receptors in kindling epileptogenesis.