Effect of a glutamate receptor antagonist (GYKI 52466) on 4-aminopyridine-induced seizure activity developed in rat cortical slices

In the present experiments we have tested the effect of the noncompetitive AMPA antagonist GYKI 52466 (20-80 mu M) on spontaneous epileptic discharges developed as the consequence of 4-aminopyridine application in neocortex s lices of adult rats. Parallel to the changes of spontaneous activity, the f ield potentials, evoked by electrical stimulation of the corpus callosum, w ere also analyzed, Glass microcapillary extracellular recording electrode w as positioned in the third layer of the somatosensory cortex slice, while t he stimulating electrode was placed at the border of the white and gray mat ter. 4-aminopyridlne and GYKI 52466 were bath-applied. The application of 4 0 mu M GYKI 52466 caused about 40% decrease in the frequency and the amplit ude of spontaneous seizures as well as the duration of each discharges deve loped in 4-aminopyridine, Pre-incubation with the AMPA antagonist effective ly inhibited both the development of seizure activity and the maintenance o f the discharges. GYKI 52466 also decreased the duration and amplitude of f ield responses evoked by stimulation of the corpus callosum. This inhibitor y effect was dose-dependent, Our data in the in vitro cortex slice epilepsy model suggest that the non-competitive AMPA antagonist GYKI 52466 is a pot ent anticonvulsant and neuroprotective compound because it reduced the full y developed epileptic discharges or prevented their development. (C) 1999 E lsevier Science Inc.