title: Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats.
abstract: Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment. The sucrose preference test and open-field test were used to assess behavioral changes. The expression levels of excitatory amino acid transporters (EAATs) were measured by western blot. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect hippocampal glutamate concentrations. We found that the expression of EAAT2 and EAAT3 were obviously downregulated, and extracellular concentrations of glutamate were significantly increased in the hippocampi of depressive-like rats. Ketamine (10, 25, and 50mg/kg) upregulated the expression of EAAT2 and EAAT3, decreased the hippocampal concentration of extracellular glutamate, and alleviated the rats' depressive-like behavior. The antidepressant effect of ketamine may be linked to the regulation of EAAT expression and the enhancement of glutamate uptake in the hippocampus of depressive-like rats.
authors.affiliation: Department of Anesthesiology, The Central Hospital of Enshi, Autonomous Prefecture, Enshi, Hubei, 445000, China. Electronic address: zhuxianlin8@sohu.com.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Central Hospital of Enshi, Autonomous Prefecture, Enshi, Hubei, 445000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, The Central Hospital of Enshi, Autonomous Prefecture, Enshi, Hubei, 445000, China. Electronic address: 343205560@qq.com.
authors.forename: Zaiping
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Hao
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D027322:Amino Acid Transport System X-AG; D000777:Anesthetics; D000928:Antidepressive Agents; D007649:Ketamine
keywords: Depression; Excitatory amino acid transporters; Glutamate reuptake; Ketamine