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In turn, hippocampal nNOS-derived nitric oxide (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)\/cGMP and peroxynitrite (ONOO<jats:sup>\u2212<\/jats:sup>)\/extracellular signal-regulated kinase signal pathways, and therefore elevated hypothalamic corticotrophin-releasing factor, a peptide that governs the hypothalamic-pituitary-adrenal axis. More importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive behaviors. In addition, directly delivering ONOO<jats:sup>\u2212<\/jats:sup>donor into hippocampus caused depressive-like behaviors. Our findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.<\/jats:p>","DOI":"10.1523\/jneurosci.0004-11.2011","type":"journal-article","created":{"date-parts":[[2011,5,25]],"date-time":"2011-05-25T16:49:08Z","timestamp":1306342148000},"page":"7579-7590","source":"Crossref","is-referenced-by-count":129,"title":["Hippocampal Neuronal Nitric Oxide Synthase Mediates the Stress-Related Depressive Behaviors of Glucocorticoids by Downregulating Glucocorticoid 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