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Thus, a systematic animal behavioral investigation was carried out in this study. This will promote the research and treatment of pruritus and depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 2,4\u2010dinitrofluorobenzene (<jats:styled-content style=\"fixed-case\">DNFB<\/jats:styled-content>)\u2010induced chronic itch model was established to measure the depression index by forced swimming test (<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>), tail suspension test (<jats:styled-content style=\"fixed-case\">TST<\/jats:styled-content>), and splash test (<jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>). The chronic unpredicted mild stress (<jats:styled-content style=\"fixed-case\">CUMS<\/jats:styled-content>)\u2010induced depression model was established to measure spontaneous itch and acute histamine or chloroquine\u2010induced itch behaviors. A depression and itch combining model was also established to measure the scratching and depression behaviors. The motor function of <jats:styled-content style=\"fixed-case\">DNFB<\/jats:styled-content> mice was analyzed by the rotarod test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The scratching number, the immobility time in the <jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TST<\/jats:styled-content>, and the grooming number in the <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content> test were all significantly increased in the chronic itch model. Mice receiving <jats:styled-content style=\"fixed-case\">CUMS<\/jats:styled-content> treatment showed significantly increased spontaneous scratching number, immobility time in the <jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TST<\/jats:styled-content> tests, and grooming number in the <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>. The combined model showed increased immobility time in <jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TST<\/jats:styled-content> tests and increased grooming number in <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content> comparing to the depression model, and showed increased scratching number comparing to the chronic itch model. After histamine (His) or chloroquine (<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>) injection, the scratching numbers of <jats:styled-content style=\"fixed-case\">CUMS<\/jats:styled-content> mice were all significantly increased compared to those of His\u2010 and <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>\u2010control, respectively. Anti\u2010depression drug ketamine could significantly inhibit the depression\u2010like behaviors of <jats:styled-content style=\"fixed-case\">CUMS<\/jats:styled-content> mice, and simultaneously stopped the promoting effect on His\u2010induced acute itch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study established an appropriate cross aggravation experimental mode and demonstrated that there is cross aggravation between pruritus and depression. The illumination of related mechanisms underlying this cross aggravation effect will provide theoretical basis for the prevention and treatment of depression and pruritus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.964","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T04:24:44Z","timestamp":1525235084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The behavioral study on the interactive aggravation between pruritus and depression"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiao\u2010Dong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anatomy and K.K. Leung Brain Research Centre The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and K.K. 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