A POMC-originated circuit regulates stress-induced hypophagia, depression, and anhedonia

Mol Psychiatry. 2020 May;25(5):1006-1021. doi: 10.1038/s41380-019-0506-1. Epub 2019 Sep 5.


Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMCARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DAVTA neurons). We further revealed that POMCARH neurons project to the VTA and provide an inhibitory tone to DAVTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMCARH→VTA circuit in mice increases body weight and food intake, and reduces depression-like behaviors and anhedonia in mice exposed to chronic restraint stress. Thus, our results identified a novel neurocircuitry regulating feeding and mood in response to stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anhedonia*
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Arcuate Nucleus of Hypothalamus / pathology
  • Depression / metabolism*
  • Feeding and Eating Disorders / etiology*
  • Feeding and Eating Disorders / metabolism*
  • Feeding and Eating Disorders / psychology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways*
  • Pro-Opiomelanocortin / metabolism*
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism*
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / pathology


  • Pro-Opiomelanocortin