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However, there are few drugs for PTSD treatment. In this study, conditioned fear and single\u2010prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal <jats:italic>Salvia miltiorrhiza<\/jats:italic>, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD\u2010like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety\u2010like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity\u2010related proteins as well as activated CREB\/BDNF\/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p\u2010CREB, BDNF, TrkB, and synaptic plasticity\u2010related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB\u2010binding protein. These findings indicate that TanIIA ameliorates PTSD\u2010like behaviors in mice by activating the CREB\/BDNF\/TrkB pathway, which provides a basis for PTSD treatment.<\/jats:p>","DOI":"10.1002\/ptr.7540","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T14:09:48Z","timestamp":1657289388000},"page":"3932-3948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Tanshinone <scp>IIA<\/scp> improves contextual fear\u2010 and anxiety\u2010like behaviors in mice via the <scp>CREB<\/scp>\/<scp>BDNF<\/scp>\/<scp>TrkB<\/scp> signaling pathway"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-6993","authenticated-orcid":false,"given":"Yong\u2010li","family":"Jiang","sequence":"first","affiliation":[{"name":"Precision Pharmacy &amp; Drug Development Center, Department of Pharmacy, Tangdu Hospital Fourth Military Medical University  Xi'an 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