Muscimol prevents neuronal injury induced by NMDA

The effect of muscimol on N-methyl-D-aspartate (NMDA)-induced injury of primary cultured cerebral cortical neurons was examined. NMDA induced a dose-dependent leakage of LDH activity, which was significantly inhibited by (+-)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclopentan-5,10-imine (MK-801). Muscimol significantly reduced the NMDA-induced increase of lactic dehydrogenase (LDH) leakage, and bicuculline abolished this protective effect of muscimol. Similarly, muscimol reduced the NMDA-induced increase in trypan blue staining of the cells, and bicuculline suppressed this inhibitory action of muscimol. These results suggest that GABAA-receptor stimulation exerts a protective action against the neuronal injury induced by NMDA-receptor activation.