NMDA Antagonist MK-801 Suppresses Behavioral Seizures, Augments Afterdischarges,but Does Not Block Development of Perforant Path Kindling

摘要

The role of N-methyl-D-aspartate (NMDA) in the development and expression ofkindled seizures was assessed using a crossover design. MK-801 produced a significant increase in afterdischarge (AD) threshold and a suppression of behavioral seizure development during the first 10 stimulations. However, upon removal of the drug, an immediate increase in seizure stage and the number of animals displaying generalized seizure signs (clonic component) was observed. Paradoxically, MK-801 also produced an increase in mean AD duration in the perforant path and dentate gyrus over the first 10 stimulations. These data indicate that MK-801 possesses anticonvulsant properties with respect to behavioral seizure, and is less effective as an antiepileptogenic agent-i.e., significant kindling development occurred with MK-801 in the absence of overt behavioral expression of the kindled response. A dissociation between seizure stage and AD duration suggests that independent mechanisms may control the electrographic and behavioral indices of kindling.