HCRT and major depressive disorder: In animal models, acute stress, including the forced swim test, restraint stress and the stress of intraperitoneal injections are associated with an upregulation of orexin activity (Chang et al., 2007; Grafe et al., 2017; Panhelainen & Korpi, 2012) while chronic stress-induced depression-like behaviour using a rat social defeat model decreases basal orexin activity (Nocjar et al., 2012).