Schaffer et al. (2010) had reported that forced expression of NOR1 in the amygadala can induce depression-like behaviors in rats, while the NOR1 gene deficiency elicits a reverse effect, suggesting that pathologically elevated NOR1 may mediate the pathogenesis of depression. This hypothesis is supported by another finding: restraint stress, which has been shown to trigger depression-like behaviors, leads to a significant increase in NOR1 mRNA expression levels in the adrenal pituitary and hypothalamus (Helbling et al., 2014) (Figure 1). Here, NR4A3 is linked to major depressive disorder.