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However, it is seldom known whether berberine produces antidepressant-like effects in ovariectomized mice, which exhibit depressive-like responses. To examine the antidepressant-like effects of berberine in ovariectomized mice, behavioral tests were conducted, including the forced swimming test and the open field test. To elucidate the mechanisms, levels of BDNF, phosphorylated CREB and phosphorylated eEF2 were analyzed by western blotting, and c-Fos induction was examined by immunohistochemistry. In the forced swimming test, berberine decreased the immobility time in a dose-dependent manner, reversing the depressive-like effect observed in ovariectomized mice, and this effect was blocked by the 5-HT<jats:sub>2<\/jats:sub>antagonist ketanserin. In addition, western blotting indicated that BDNF and peEF<jats:sub>2<\/jats:sub>in the hippocampus, but not pCREB\/CREB in the frontal cortex, were affected by berberine treatment. Furthermore, immunohistochemistry demonstrated that the reduction in c-Fos induced by ovariectomy were greater after berberine treatment. Ketanserin also antagonized the effect of berberine on the c-Fos expression. Our findings suggest that berberine exerts antidepressant-like effects in ovariectomized mice, and 5-HT<jats:sub>2<\/jats:sub>receptor activation may be partially related to the antidepressant-like effects of the berberine by BDNF-CREB and eEF<jats:sub>2<\/jats:sub>pathways.<\/jats:p>","DOI":"10.1038\/s41598-017-01035-5","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T10:29:08Z","timestamp":1493116148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Berberine produces antidepressant-like effects in ovariectomized mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Jie","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Mlyniec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranji","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,2]]},"reference":[{"key":"1035_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1001\/archpsyc.62.6.617","volume":"62","author":"RC Kessler","year":"2005","unstructured":"Kessler, R. 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