title: Changes in hippocampal AMPA receptors and cognitive impairments in chronic ketamine addiction models: another understanding of ketamine CNS toxicity.
abstract: Ketamine has been reported to impair human cognitive function as a recreational drug of abuse. However, chronic effects of ketamine on central nervous system need to be further explored. We set out to establish chronic ketamine addiction models by giving mice a three or six month course of daily intraperitoneal injections of ketamine, then examined whether long-term ketamine administration induced cognition deficits and changed hippocampal post-synaptic protein expression in adult mice. Behavior tests results showed that mice exhibited dose- and time-dependent learning and memory deficits after long-term ketamine administration. Western blot results showed levels of GluA1, p-S845 and p-S831 proteins demonstrated significant decline with ketamine 60 mg/kg until six months administration paradigm. But levels of p-S845 and p-S831 proteins exhibited obvious increase with ketamine 60 mg/kg three months administration paradigm. NR1 protein levels significantly decrease with ketamine 60 mg/kg three and six months administration paradigm. Our results indicate that reduced expression levels and decreased phosphorylation levels of hippocampal post-synaptic membrane GluA1- containing AMPA receptors maybe involved in cognition impairment after long-term ketamine administration. These findings provide further evidence for the cognitive damage of chronic ketamine addiction as a recreational drug.
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.|Department of Forensic and Medical Laboratory, Jining Medical University, 16 Hehua Road, Jining 272067, P. R. China.|Center of Forensic Science Jining Medical University, Jining Medical University, 16 Hehua Road, Jining 272067, P. R. China.
authors.forename: Runtao
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Ao
authors.initials: A
authors.lastname: Du
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Bolin
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Shen
authors.affiliation: Key Laboratory of Health Ministry in Congenital Malformation, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China.
authors.forename: Jichuan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Forensic and Medical Laboratory, Jining Medical University, 16 Hehua Road, Jining 272067, P. R. China.|School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan, Shandong 250062, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic and Medical Laboratory, Jining Medical University, 16 Hehua Road, Jining 272067, P. R. China.|Center of Forensic Science Jining Medical University, Jining Medical University, 16 Hehua Road, Jining 272067, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Health Ministry in Congenital Malformation, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D003072:Cognition Disorders / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D007649:Ketamine