The role of the orexin system in stress response

Neuropharmacology. 2019 Aug;154:68-78. doi: 10.1016/j.neuropharm.2018.09.034. Epub 2018 Sep 25.


Orexins are neuropeptides that are exclusively produced by hypothalamic neurons, which project throughout the entire brain. Orexin, also known as hypocretins, were initially identified to play a fundamental role in food intake, arousal and the regulation of sleep and wakefulness. Recent studies identified orexins to be critical for diverse physiological processes including motivation, reward, attention, emotional regulation, stress and anxiety. Here, I review recent findings that indicate orexin has an important role in acute and chronic stress. I also summarize the recent optogenetic and chemogenetic studies that have advanced our understanding of the orexin system. I will conclude by discussing clinical studies that implicate orexins in mental health disorders. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.

Keywords: Anxiety; Hypocretin; Hypothalamus; Optogenetics; Orexin; Stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Arousal / physiology
  • Brain / metabolism*
  • Humans
  • Orexin Receptors / physiology*
  • Orexins / physiology*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology*
  • Wakefulness / physiology


  • Orexin Receptors
  • Orexins