Glutamate receptor antagonists reduce spontaneous epileptiform activity in cortical wedges prepared from DBA/2 mice.
This study investigated the involvement of glutamatergic neurotransmission in the epileptiform activity demonstrated in cortical weges prepared from genetically audiogenic seizure-prone DBA/2 mice. Omission of Mg2+ from the perfusing medium initiated spontaneous epileptiform events with accompanying afterpotentials on the repolarizing phase. These spontaneous depolarizations also occurred in some 30% of the slices in the presence of Mg2+ (2 mM). The N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxypiperazin-4-yl)-propenyl-1-phosphonic acid (CPP) and the non-competitive NMDA receptor channel blocker ketamine produced a significant reduction of these spontaneous depolarizations. 7-Chlorokynurenic acid (7-CKA), an antagonist at the strychnine-insensitive site on the NMDA receptor, also exerted an inhibitory effect. In addition the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) suppressed the spontaneous events. These observations provide evidence that glutamatergic neurotransmission contributes to the epileptiform activity in this cortical preparation.
Hu
R Q
RQ
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Davies
J A
JA
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D004827:Epilepsy / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D008274:Magnesium