A selective N-methyl-D-aspartate antagonist depresses epileptiform activity in rat hippocampal slices

The sensitivity of convulsant-induced epileptiform activity in the hippocampus to the selective N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5-phosphonovalerate (D-APV) was examined using in vitro electrophysiological techniques. This compound reduced the number and size of the synaptically evoked population spikes recorded in the CA1 region in the presence of the convulsants, pentylenetetrazol, bicuculline or folate. Intracellular recordings in the presence of bicuculline showed that D-APV reduced the late component of the excitatory postsynaptic potential and the number of action potentials evoked synaptically. A mechanism is suggested to explain how NMDA receptors, which are known not to be involved in normal synaptic transmission in hippocampal slices, can contribute to epileptiform activity.