Rapid glucocorticoid effects on excitatory amino acid levels in the hippocampus: a microdialysis study in freely moving rats

Glucocorticoids can rapidly affect neuronal function and behaviour in mamma ls. Several studies have suggested the possible existence of rapid, non-gen omic effects of glucocorticoids in the hippocampus. To investigate whether glucocorticoids could affect neurotransmission in the hippocampus through r apid, non-genomic mechanisms, we studied the effects of acute glucocorticoi d administration on extracellular amino acid levels in the CA1 area of the hippocampus. By means of microdialysis on freely moving rats, we observed t hat an intraperitoneal injection of corticosterone (2.5 mg/kg) induced a ra pid (within 15 min) and transient (returning to basal levels by 35-45 min) increase in extracellular aspartate and glutamate levels (similar to 155-16 0%), both in sham-operated and adrenalectomized rats. These effects occurre d in parallel with a rise in corticosterone concentration, also detected by microdialysis, in this hippocampal area. Intrahippocampal perfusion of cor ticosterone by retrodialysis also produced the same fast and reversible eff ects on excitatory amino acid (EAA) levels. Extracellular concentrations of taurine and gamma-aminobutyric acid (GABA) were unchanged after intrahippo campal glucocorticoid administration. This corticosterone-mediated rise in EAA levels was not inhibited by the presence of specific antagonists for th e two types of intracellular corticosteroid receptors, nor by a protein syn thesis inhibitor, anisomycin. Perfusion of dexamethasone, a synthetic gluco corticoid, elicited a similar effect to that observed with corticosterone t reatment in all studied cases. However, non-glucocorticoid steroids did not affect amino acid transmission in this hippocampal area. These results ind icate that glucocorticoids induce a rapid and transient increase in hippoca mpal EAA levels in vivo that might be exerted through a novel non-genomic m echanism of action.