Therefore, although a variety of chronic stressors, such as repeated tail pinch, daily restraint, chronic unpredictable stress and CSDS in rats and mice, cause persistent elevation in plasma ghrelin, the resulting potentiation of ghrelin/GHS-R1a system seems to play distinct roles, either maladaptive or adaptive, in the development of increased vulnerability to anxiety and depression after chronic stress exposure. Here, GHRL is linked to major depressive disorder.