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After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1\/2, AKT, and AMPK. Adult female C57BL\/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10\u00a0mg\/kg), and FR180204 (ERK1\/2 inhibitor, i.p.100\u00a0mg\/kg)\u2009+\u2009ketamine group. Three mice randomly selected from each group were injected with\n                    <jats:sup>18<\/jats:sup>\n                    F-FDG at 6\u00a0h after treatment. The brain tissue was collected at 6\u00a0h after treatment for p-ERK1\/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), and the immobility time was significantly shortened in depressive-like mice (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). An ERK1\/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), as well as prolonged the immobility time (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). The expression levels of p-ERK1\/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1\/2 and GLUT3 in the prefrontal cortex (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01), whereas an ERK1\/2 inhibitor significantly inhibited ketamine-induced increases (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK\/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-97758-7","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T06:04:04Z","timestamp":1631513044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK\/GLUT3 signaling pathway"],"prefix":"10.1038","volume":"11","author":[{"given":"Xin","family":"Ouyang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maozhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianGuo","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"97758_CR1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1126\/science.1222939","volume":"338","author":"RS Duman","year":"2012","unstructured":"Duman, R. 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