Citation:

Gilbert, M. NMDA ANTAGONIST MK-801 SUPPRESSES BEHAVIORAL SEIZURES, AUGMENTS AFTERDISCHARGES, BUT DOES NOT BLOCK DEVELOPMENT OF PERFORANT PATH KINDLING. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/414 (NTIS PB95125324), 1994.

Description:

The role of the N-methyl-d-aspartate (NMDA) in the development and expression of kindled seizures was assessed using a crossover design. ats were stimulated once daily in the perforant path for 10 consecutive days following administration of saline or the NMDA antagonist MK-801 (1.0 mg/kg). ive to ten days elapsed prior to an additional 10 stimulations with the drug groups reversed. eparate group of animals was stimulated following saline administration for 20 days. K-801 produced a significant increase in AD threshold and a suppression of behavioral seizure development during the first 10 stimulations. owever, upon removal of the drug, an immediate increase in seizure stage and the number of animals displaying generalized seizure signs (clonic component) was observed. K-801 also produced an increase in mean AD duration in the perforant path and dentate gyrus over the first 10 stimulations. pon reversal of the dose groups in phase II of the study, AD duration increased in animals treated with MK-801 for the first time, and decreased in animals taken off MK-801 and stimulated drug free. he augmentation in AD associated with MK-801 was partially attributed to an increase in rebound AD. t was concluded that although MK-801 possesses strong anticonvulsant properties with respect to behavioral seizure, it is not an effective antiepileptic agent - significant kindling development occurred with MK-801 in the absence of overt behavioral expression of the kindled response. issociation between seizure stage and AD duration suggests that independent mechanisms may control the electrographic and behavioral indices of kindling.

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