In order to elucidate the mechanism of the cytotoxic effect of glucocorticoid on the rat hippocampus, we studied the effects of dexamethasone, a synthetic glucocorticoid, on neurotransmitter release from the hippocampus by in vivo microdialysis. Dexamethasone (10 mg/kg) was administered i.p. and the extracellular concentrations of the amino acids (glutamate, aspartate, glycine), GABA and acetylcholine were determined in the hippocampus of freely moving rats. Glutamate concentration increased by 20-25% after dexamethasone administration and this effect continued for 1 hour. The extracellular concentration of the other neurotransmitters, however, did not show any significant changes. From these results, we concluded that increased extracellular glutamate may be involved, at least in part, in the cytotoxic effect of glucocorticoid on hippocampal neurons.

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