Orexin prevents depressive-like behavior by promoting stress resilience

• DOI: 10.1038/s41380-018-0127-0
• Publication Date: 2018-08-07T11:16:45Z
• Authors: Miao-Jin Ji; Xiao-Yang Zhang; Zi Chen; Jian-Jun Wang; Jing-Ning Zhu
• Keywords: Lateral hypothalamus; Orexin receptor

Hypothalamic neuropeptide orexin has been implicated in the pathophysiology of psychiatric disorders and accumulating clinical evidence indicates a potential link between depression. However, exact role depression, particularly underlying neural substrates mechanisms, remains unknown. In this study, we reveal direct projection from hypothalamic orexinergic neurons to ventral pallidum (VP), structure that receives an increasing attention for its critical position rewarding processing, stress responses, We find directly excites GABAergic VP prevents depressive-like behaviors rats. Two receptors, OX1R OX2R, their downstream Na+–Ca2+ exchanger L-type Ca2+ channel co-mediate effect orexin. Furthermore, pharmacological blockade or genetic knockdown receptors increases forced swim test sucrose preference test. Intriguingly, blockage inputs no impact on social proximity interaction novel partners, but remarkably strengthens avoidance under acute psychosocial triggered by rank. Notably, significantly increased level is accompanied increase serum corticosterone animals exposed stresses, including swimming, food/water deprivation rank stress, rather than non-stress situations. These results suggest endogenous modulation especially protecting against depressive reactions stressful events. The findings define indispensable central system preventing depression promoting resilience.