Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance

Adam J. Walker, Brittany M. Foley, Shari L. Sutor, Jane A. McGillivray, Mark A Frye, Susannah J Tye

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Ketamine, N-methyl- d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100. μg/d or saline (0.9%) for 14. d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10. mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.

Original languageEnglish (US)
Pages (from-to)198-202
Number of pages5
JournalBehavioural Brain Research
Volume293
DOIs
StatePublished - Oct 5 2015

Keywords

  • Adrenocorticotropic hormone (ACTH)
  • Animal model
  • C-reactive protein (CRP)
  • Cytokine
  • Ketamine
  • Treatment-resistant depression (TRD)

ASJC Scopus subject areas

  • Behavioral Neuroscience

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