HCRT and major depressive disorder: For example, it has been demonstrated that Wistar–Kyoto rats, long-regarded as a genetic model of depression based on enhanced sensitivity to stress and reduced sensitivity to selective serotonin reuptake inhibitors (SSRIs; Lopez-Rubalcava and Lucki, 2000), exhibit reduced numbers of orexin neurons, as well as smaller soma size, lower prepro-orexin mRNA expression, and lower OXA levels in various brain areas (Taheri et al., 2001; Allard et al., 2004).