DEVELOPMENT DISSOCIATION OF PHARMACOLOGICAL AND NEUROTOXIC EFFECTS OF EXCITATORY AMINO-ACIDS

The development of excitatory amino acid-(EAA)-induced cytotoxic cell death and [H-3]gamma-aminobutyric acid ([H-3]GABA) release were simultaneously examined in primary cultures of the rat cerebral cortex. Pronounced [H-3]GABA release could already be evoked on day 3 by N-methyl-D-aspartate, quisqualate and kainate, whereas toxic cell death could first be induced on day 7, in vitro. EAA-induced GABA release declined between day 11 and 14, but the excitotoxic vulnerability of cells increased further during the same period. This dissociation of releasing and toxic responses indicates that functionally active EAA receptors do not necessarily mediate excitotoxic effects and suggests that the development of EAA receptors mediating release responses precedes the maturation of intracellular mechanisms involved in excitotoxic neuronal injury, at least in cultured cortical neurons.