The NMDA-receptor antagonist, MK-801, suppresses limbic kindling and kindled seizures

Abstract

Excitatory amino acid receptors in the mammalian central nervous system (CNS) are divided into 3 receptor subtypes: kainate, quisqualate, and N-methyl- d-aspartate (NMDA). MK-801 is a selective, non-competitive antagonist of excitatory amino acid transmitters at the NMDA receptor site. The role of excitatory amino acid neurotransmission in electrical kindling was examined in animals stimulated daily in the amygdala following i.p. administration of low dosages of MK-801 (0.1 and 0.5 mg/kg). A second experiment evaluated the anticonvulsant properties of MK-801 in rats kindled in the hippocampus and amygdala, and contrasted its efficacy with the antiepileptic agents, diazepam, phenobarbital and phenytoin, and the dissociative anesthetics phencyclidine and ketamine. MK-801 (0.5 mg/kg) retarded the development of amygdala kindling and reduced mean AD duration over the first 10 stimulation sessions. The low dosage reduced total AD accrued during each kindling stage but failed to alter kindling rate. MK-801 blocked motor seizures induced by stimulation of hippocampal or amygdala kindled foci, but was more effective in reducing seizure severity and AD duration resulting from stimulation of the hippocampal focus. All other drugs tested, with the exception of phenytoin, protected against amygdaloid kindled seizures. It was concluded that excitatory amino acid transmission contributes in an important, but non-critical way to amygdala kindling.