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Here, we established a model of long\u2010term (6\u2009months) ketamine administration in wild\u2010type (C57BL\/6) mice. We elucidated the pathological effects of ketamine in the bladder and investigated changes in autophagy\u2010associated protein expression (i.e., LC3, Beclin\u20101, and P62) and inflammatory cytokines (i.e., IL\u20106 and IL\u20101\u03b2) in the bladder smooth muscle tissue. Long\u2010term ketamine administration reduced the number of layers in the bladder mucosal epithelial cells (4\u20135 layers in the saline group vs. 2\u20133 layers in the ketamine groups), but increased the number of mast cells and collagen fibers. LC3\u2010II\/LC3\u2010I, Beclin\u20101, IL\u20106, and IL\u20101\u03b2 protein expression in the bladder smooth muscle tissues of ketamine\u2010treated mice was significantly increased. The mRNA and protein levels of P62 in the Ket\u201060\u2009mg\/kg group were also significantly increased, but not the Ket\u201030\u2009mg\/kg group. Our results reveal that long\u2010term ketamine administration can cause cystitis\u2010like pathological changes in mice, and the disordered autophagy in the bladder tissue may be involved in the persistent bladder damage following long\u2010term administration of ketamine at 60\u2009mg\/kg.<\/jats:p>","DOI":"10.1002\/tox.23365","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T14:07:00Z","timestamp":1630937220000},"page":"2521-2529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Long\u2010term ketamine administration induces bladder damage and upregulates autophagy\u2010associated proteins in bladder smooth muscle tissue"],"prefix":"10.1002","volume":"36","author":[{"given":"Yanning","family":"Li","sequence":"first","affiliation":[{"name":"School of Forensic Medicine China Medical University  Shenyang China"},{"name":"School of Basic Medicine Gannan Medical University  Ganzhou 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