Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate.

The hippocampal damage caused by stress has been attributed to an increased glutamatergic tone brought about by secretion of glucocorticoids. Although exposure to stress has been shown to increase the outflow of glutamate, direct involvement of glucocorticoid in this phenomenon has not been examined. The present study demonstrates that adrenalectomy attenuates the stress-induced outflow of glutamate in the hippocampus and prefrontal cortex and that glucocorticoid replacement abolishes this attenuation.