The WAG/Rij rat model for nonconvulsive absence epilepsy: involvement of nonNMDA receptors.
The involvement of AMPA and kainate receptors in nonconvulsive epilepsy was studied by intracerebroventricular injections of AMPA, GDEE, kainic acid and kynurenic acid in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations showed that AMPA (0.1 pmol/5 microliters; 1 pmol/5 microliters; 10 pmol/5 microliters) dose-dependently increased the nonconvulsive absence epilepsy while GDEE (0.2 mumol/5 microliters; 1 mumol/5 microliters; 5 umol/5 microliters) caused a dose-dependent decrease. All effects of GDEE could be blocked by an inactive AMPA dosage. Kainic acid (0.01 nmol/5 microliters; 0.1 nmol/5 microliters; 0.15 nmol/5 microliters) had no effects on the nonconvulsive epilepsy but induced convulsions in the two highest dosages. Kynurenic acid (50 nmol/5 microliters; 100 nmol/5 microliters; 500 nmol/5 microliters) decreased dose-dependently the incidence of nonconvulsive epilepsy. The effect of kynurenic acid could be blocked by a nonconvulsive dosage of kainic acid. These results show that the AMPA and kainate receptor appear to be involved in nonconvulsive epilepsy. Furthermore, blockage of these two receptor subtypes led to an antiepileptic effect without inducing behavioural alterations. Therefore, selective AMPA and kainate receptor antagonists might be potent anti-epileptics.
Peeters
B W
BW
Department of Neuropharmacology, Organon International B. V., Oss, The Netherlands.
Ramakers
G M
GM
Vossen
J M
JM
Coenen
A M
AM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains / Q000502:physiology*; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D005971:Glutamates; D007608:Kainic Acid; D007736:Kynurenic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C011829:glutamic acid diethyl ester