title: Involvement of GSK3β/β-catenin signaling in the impairment effect of ketamine on spatial memory consolidation in rats.
abstract: The cellular mechanisms underlying amnesia produced by the analgesic ketamine are not clear. The current study examined the effects of ketamine on memory consolidation in rats trained in a Morris water maze task, and further tested whether the glycogen synthase kinase (GSK)3β/β-catenin signaling pathway was involved in mediating the effects of posttraining ketamine on retention. Adult male Sprague-Dawley rats were injected with ketamine (0, 25, 50, or 100mg/kg) immediately after an eight-trial water maze training session. A probe trial was carried out 24 h later to examine the effects of ketamine on memory. Rats hippocampi were subjected to western blot assays to measure levels of native versus phosphorylated (p) GSK3β and β-catenin protein. Memory performance was significantly impaired in rats injected with ketamine (100 mg/kg) after training. Western blots showed that p-GSK-3β(Ser9) levels were reduced and p-β-catenin(Ser33/37/Thr41) levels were elevated in ketamine treated rats during consolidation. These posttraining changes in hippocampal p-GSK-3β and p-β-catenin were blocked by injection of 100mg/kg ketamine immediately after training, indicating that the 100mg/kg dose of ketamine altered activation of GSK3β/β-catenin signaling pathway in the hippocampus. Acute injection of the GSK3β specific inhibitor SB216763 (1 ng/0.5 μl/side) into area CA1 of the hippocampus after water maze training prevented ketamine-induced impairment of memory and blocked ketamine-induced effects on the GSK3β/β-catenin signaling pathway in the hippocampus. Our results suggest that an anesthetic dose of ketamine injected immediately after Morris water maze training impaired memory consolidation and support the hypothesis that GSK3β/β-catenin signaling may play a role in ketamine-induced retrograde amnesia.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: 38513345@qq.com.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: xuguanghong2004@163.com.
authors.forename: Guang-Hong
authors.initials: GH
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: wangkai1964@126.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. Electronic address: caojl0310@aliyun.com.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: ay_guew_mz@163.com.
authors.forename: Er-Wei
authors.initials: EW
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: liyuanhai-1@163.com.
authors.forename: Yuan-Hai
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: liu711029@hotmail.com.
authors.forename: Xue-Sheng
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000778:Anesthetics, Dissociative; D051176:beta Catenin; D007649:Ketamine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3
keywords: Glycogen synthase kinase-3β; Ketamine; Memory consolidation; Morris water maze; β-Catenin