Medium-dependent dissociation of cytotoxic and GABA-releasing effects of N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate in rat cortical cultures

The excitotoxic cell death and the release of gamma-amino-butyric acid (GABA) evoked by excitatory amino acids (EAAs) were comparatively examined in rat cortical sister cultures grown in serum-free (N2) and serum-supplemented (SSM) media. Cell death was induced by 24 h exposure to 1 mM N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or kainate. [3H]GABA release was evoked by 5 min exposure of preloaded cultures to 0.5 mM NMDA, AMPA or kainate. EAAs evoked remarkable GABA release in both N2 and SSM cultures, but caused toxic cell death in SSM cultures, only. Our findings indicate that functionally active EAA receptors do not necessarily mediate neurotoxicity and suggest that excitotoxicity can be prevented without blocking excitatory transmission.