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Adult male Sprague\u2010Dawley rats received either a chronic systemic administration of CORT (daily 25 mg\/kg in sesame oil, subcutaneously) or long\u2010term bilateral adrenalectomy (ADX) (3\u20134 weeks), and then the release of 4\u2010aminopyridine (4AP)\u2010evoked endogenous glutamate and the levels of glucocorticoid receptor (GR) expression from hippocampal nerve terminals were studied. Chronic administration of CORT resulted in a significant increase of 4AP\u2010evoked glutamate release from hippocampal nerve terminals, whereas ADX reduced 4AP\u2010evoked glutamate release. In addition, chronic administration of CORT and ADX induced a significant reduction and increase in GR expression in hippocampal synaptosomes, respectively, as detected by Western blots. Furthermore, acute treatment of CORT or dexamethasone facilitated 4AP\u2010evoked glutamate release from synaptosomes freshly isolated from na\u00efve rat hippocampus and this effect can be significantly prevented by pretreatment of GR antagonist mifepristone, but not by mineralocorticoid receptor (MR) antagonist RU28318. Together, our results strongly support the presence of GRs on presynaptic nerve terminals in the rat hippocampus acting to facilitate the release of neuronal glutamate. Synapse 63:745\u2013751, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.20654","type":"journal-article","created":{"date-parts":[[2009,5,29]],"date-time":"2009-05-29T19:10:22Z","timestamp":1243624222000},"page":"745-751","source":"Crossref","is-referenced-by-count":58,"title":["Modulation of presynaptic glucocorticoid receptors on glutamate release from rat hippocampal nerve 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