title: The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus.
abstract: OBJECTIVE
  Active inflammatory responses play an important role in the pathogenesis of depression. We hypothesized that the rapid antidepressant effect of ketamine is associated with the down-regulation of pro-inflammatory mediators.
  
  
  METHODS
  Forty-eight rats were equally randomized into six groups (a control and five chronic unpredictable mild stress (CUMS) groups) and given either saline or 10 mg/kg ketamine, respectively. The forced swimming test was performed, and the hippocampus was subsequently harvested for the determination of levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP).
  
  
  RESULTS
  CUMS induced depression-like behaviours and up-regulated the hippocampal levels of IL-1β, IL-6, TNF-α, IDO, and the KYN/TRP ratio, which were attenuated by a sub-anaesthetic dose of ketamine.
  
  
  CONCLUSIONS
  CUMS-induced depression-like behaviours are associated with a reduction in hippocampal inflammatory mediators, whereas ketamine's antidepressant effect is associated with a down-regulation of pro-inflammatory cytokines in the rat hippocampus.
authors.affiliation: a 1 Department of Anesthesiology, The Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University , Nanjing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: b 2 Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military , Changzhou, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Yu
authors.affiliation: a 1 Department of Anesthesiology, The Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University , Nanjing, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Shen
authors.affiliation: b 2 Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military , Changzhou, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Gao
authors.affiliation: b 2 Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military , Changzhou, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: c 3 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University , Nanjing, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: c 3 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University , Nanjing, China.
authors.forename: Guang-Fen
authors.initials: GF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D013550:Swimming / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine
keywords: Depression; indoleamine 2,3-dioxygenase; ketamine; kynurenine; tryptophan