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To investigate the antidepressant-like activity of propolis extract, CD-1 mice were administered an ethanol extract of propolis (50, 100, or 200\u2009mg\/kg, p.o.) prior to the behavioral test. The propolis extract-treated group showed a dose-dependent decrease in immobility time in the FST and tail suspension test without altering locomotor activity. Propolis extract decreased the limbic hypothalamic-pituitary-adrenal axis response to the FST as indicated by an attenuated corticosterone response and decreased in c-fos immunoreactive neurons in the hippocampal dentate gyrus. Western blot analysis revealed a reduction in hippocampal glucocorticoid receptor (GR) expression following the FST, which was reversed by propolis extract. Propolis extract also increased pGR(S220)\/(S234) ratio by a differential phosphorylation in S220 and S234. FST-induced downregulation of cAMP-responsive element binding protein phosphorylation at S133 (pCREB) was restored by propolis extract, showing a strong and positive relationship between pCREB and pGR(S220)\/(S234) ratio. These findings suggest that the propolis extract potentiates antidepressant-like activity by enhancing GR function which is one of the therapeutic mechanisms of antidepressant; thus, propolis extract may provide a novel therapy for depression.<\/jats:p>","DOI":"10.1155\/2013\/217853","type":"journal-article","created":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T17:03:35Z","timestamp":1371661415000},"page":"1-10","source":"Crossref","is-referenced-by-count":14,"title":["Novel Antidepressant-Like Activity of Propolis Extract Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus"],"prefix":"10.1155","volume":"2013","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0953-0003","authenticated-orcid":true,"given":"Mi-Sook","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Republic of Korea"},{"name":"Acupuncture & Meridian Science Research Center, College of 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