DOI: 10.1093/ijnp/pyad069 ISSN: 1461-1457

Chronic stress-induced elevation of melanin-concentrating hormone in the locus coeruleus inhibits norepinephrine production and associated with depression-like behaviors in rats

Nurhumar Kurban, Yu Qin, Hui-Ling Zhao, Xiao Hu, Xi Chen, Yi-Yi Zhao, Yu-Shuo Peng, Hong-Bo Wang, Su-Ying Cui, Yong-He Zhang
  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Pharmacology



Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that projects throughout the central nervous system, including the noradrenergic locus coeruleus (LC). Our previous study suggested that MCH/MCH receptor 1 (MCHR1) in the LC may be involved in the regulation of depression. The present study investigated whether the role of MCH/MCHR1 in the LC in depression-like behaviors is associated with the regulation of norepinephrine.


Chronic unpredictable stress (CUS) and an acute intra-LC microinjection of MCH induced depression-like behaviors in rats. The MCHR1 antagonist SNAP-94847 was also microinjected in the LC in rats that were suffered CUS or treated with MCH. The sucrose preference, forced swim, and locomotor tests were used for behavioral evaluation. Immunofluorescence staining, ELISA, western blot and HPLC-ECD were used to explore the mechanism of MCH/MCHR1 in the regulation of depression-like behaviors.


CUS induced an abnormal elevation of MCH levels and downregulated MCHR1 in the LC, which was highly correlated with the formation of depression-like behaviors. SNAP-94847 exerted antidepressant effects in CUS-exposed rats by normalizing tyrosine hydroxylase, dopamine β hydroxylase, and norepinephrine in the LC. An acute microinjection of MCH induced depression-like behaviors through its action on MCHR1. MCHR1 antagonism in the LC significantly reversed the MCH-induced downregulation of norepinephrine production by normalizing MCHR1-medicated cAMP-PKA signaling.


Our study confirmed that the MCH/MCHR1 system in the LC may be involved in depression-like behaviors by downregulating norepinephrine production. These results improve our understanding of the pathogenesis of depression that is related to the MCH/MCHR1 system in the LC.

More from our Archive