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

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)-1, IL-6, tumour necrosis factor- (TNF-), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP).Results. CUMS induced depression-like behaviours and up-regulated the hippocampal levels of IL-1, IL-6, TNF-, 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.