Interactions of the orexin/hypocretin neurones and the histaminergic system

Acta Physiol (Oxf). 2015 Feb;213(2):321-33. doi: 10.1111/apha.12432. Epub 2014 Dec 29.


Histaminergic and orexin/hypocretin systems are components in the brain wake-promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.

Keywords: autoimmune; histamine; hypocretin/orexin; mouse; narcolepsy; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Histamine / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Narcolepsy / metabolism*
  • Narcolepsy / physiopathology
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Orexins
  • Wakefulness / physiology


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Histamine