A slow intravenous infusion of N-methyl-DL-aspartate as a seizure model in the mouse.
A seizure model involving slow i.v. infusion of the excitatory amino acid N-methyl-DL-aspartate (NMDLA) in the mouse is described. It allows determination of the threshold doses of NMDLA required to elicit clonic and tonic seizures in individual mice. The NMDA receptor antagonists MK-801, CPP, ifenprodil and 7-chlorokynurenic acid (7-CLK), and diazepam dose-dependently increased the dose of NMDLA required to elicit a tonic seizure. CPP, 7-CLK and diazepam also increased the dose of NMDLA inducing clonic seizures. In contrast, ifenprodil at doses which antagonised tonic seizures had no effect on clonic seizures. The glycine and polyamine modulatory site agonists, D-serine and spermidine respectively, dose-dependently reduced the dose of NMDLA required to induce clonic and tonic seizures. The NMDLA infusion model appears to be more sensitive than the classical bolus injection test and can detect both anticonvulsant and proconvulsant actions mediated by the NMDA receptor complex.
Singh
L
L
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, U.K.
Oles
R J
RJ
Vass
C A
CA
Woodruff
G N
GN
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D012694:Serine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology
D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D016202:N-Methylaspartate; D013095:Spermidine