Intracellular and extracellular recordings from CA3 hippocampal neurons in vitro were used to study the ability of several NMDA (N-methyl-D-aspartate) receptor antagonists to suppress epileptiform bursts induced by NMDA and convulsants not thought to act at NMDA receptors. The antagonists, APV (D-2-amino-5-phosphonovalerate), AP-7 (D,L-2-amino-7-phosphonohepatanoate) and CPP (D,L-3[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid), blocked the spontaneous and evoked bursts induced by NMDA. CPP, but not APV or AP-7, prevented the development of bursts induced by Mg-free medium. The NMDA antagonists failed to block bursting induced by kainate, 7 mM K+, mast cell degranulating peptide, anoxia or spontaneous bursting. In some cases the NMDA antagonists induced spontaneous bursts or enhanced burst frequency, a proconvulsant effect. It is concluded that activation of NMDA receptors is sufficient but not necessary for burst generation in the CA3 region.
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