TNF and major depressive disorder: For example, in animal models of chronic unpredictable stress there is evidence that depression-like behaviors are accompanied by the hippocampal upregulation of inflammatory markers, such as of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), indoleamine 2,3-dioxygenase (IDO), and kynurenine (KYN)/tryptophan (TRP) ratio, which can be attenuated by the administration of sub-anesthetic doses of ketamine [69].