IMMUNOHISTOCHEMICAL EVIDENCE FOR FLUPIRTINE ACTING AS AN ANTAGONIST ON THE N-METHYL-D-ASPARTATE AND HOMOCYSTEIC ACID-INDUCED RELEASE OF GABA IN THE RABBIT RETINA

When rabbit retinas are exposed in vitro to specific excitatory amino acid receptor agonists certain GABAergic amacrine cells are activated to cause a release of GABA. The GABA that is not released can be detec ted by immunohistochemistry. Exposure of tissues to kainate or NMDA ea ch caused a characteristic change in the GABA immunoreactivity. CNQX a ntagonised the kainate effect specifically while MK-801 counteracted t he influence of NMDA The effect produced by kainate was mimicked by do moic acid while the influence of homocysteic acid was identical with N MDA. Flupirtine alone did not influence the nature of the GABA immunor eactivity and so did not act as a kainate or NMDA agonist. However, fl upirtine counteracted the influence produced by NMDA and homocysteic a cid but had no effect on the kainate and domoic acid responses. Thus i n this system flupirtine acts as an NMDA antagonist.