GLUTAMATE-RECEPTOR ANTAGONISTS REDUCE SPONTANEOUS EPILEPTIFORM ACTIVITY IN CORTICAL WEDGES PREPARED FROM DBA 2 MICE/

This study investigated the involvement of glutamatergic neurotransmis sion in the epileptiform activity demonstrated in cortical weges prepa red from genetically audiogenic seizure-prone DBA/2 mice. Omission of Mg2+ from the perfusing medium initiated spontaneous epileptiform even ts with accompanying afterpotentials on the repolarizing phase. These spontaneous depolarizations also occurred in some 30% of the slices in the presence of Mg2+ (2 mM). The N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxypiperazin-4-yl)-propenyl-1-phosphonic acid (CP P) and the non-competitive NMDA receptor channel blocker ketamine prod uced a significant reduction of these spontaneous depolarizations. 7-C hlorokynurenic acid (7-CKA), an antagonist at the strychnine-insensiti ve site on the NMDA receptor, also exerted an inhibitory effect. In ad dition the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3 -dione (DNQX) suppressed the spontaneous events. These observations pr ovide evidence that glutamatergic neurotransmission contributes to the epileptiform activity in this cortical preparation.