The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

  • Nan Wang Department of Anesthesiology, The Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China
  • Hai-Ying Yu Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military, Changzhou, China
  • Xiao-Feng Shen Department of Anesthesiology, The Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China
  • Zhi-Qin Gao Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military, Changzhou, China
  • Chun Yang Department of Psychiatry, PLA 102nd Hospital and Mental Health Center of Military, Changzhou, China
  • Jian-Jun Yang Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
  • Guang-Fen Zhang Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
Keywords: Depression, indoleamine 2,3-dioxygenase, ketamine, kynurenine, tryptophan

Abstract

Objectives. 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)-1b, IL-6, tumour necrosis factor-a (TNF-a), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP).

Results. CUMS induced depression-like behaviours and up-regulated the hippocampal levels of IL-1b, IL-6, TNF-a, IDO, and the KYN/TRP ratio, which were attenuated by a sub-anaesthetic dose of ketamine.

Conclusion. 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.

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Published
2015-07-28
How to Cite
Wang, N., Yu, H.-Y., Shen, X.-F., Gao, Z.-Q., Yang, C., Yang, J.-J., & Zhang, G.-F. (2015). The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus. Upsala Journal of Medical Sciences, 120(4). https://doi.org/10.3109/03009734.2015.1060281
Section
Original Articles