Function and dysfunction of hypocretin/orexin: an energetics point of view

Annu Rev Neurosci. 2014:37:101-16. doi: 10.1146/annurev-neuro-071013-013855. Epub 2014 Apr 24.


The basic elements of animal behavior that are critical to survival include energy, arousal, and motivation: Energy intake and expenditure are fundamental to all organisms for the performance of any type of function; according to the Yerkes-Dodson law, an optimal level of arousal is required for animals to perform normal functions; and motivation is critical to goal-oriented behaviors in higher animals. The brain is the primary organ that controls these elements and, through evolution, has developed specialized structures to accomplish this task. The orexin/hypocretin system in the perifornical/lateral hypothalamus, which was discovered 15 years ago, is one such specialized area. This review summarizes a fast-growing body of evidence discerning how the orexin/hypocretin system integrates internal and external cues to regulate energy intake that can then be used to generate sufficient arousal for animals to perform innate and goal-oriented behaviors.

Keywords: energy balance; hypocretin; hypocretin/orexin; motivational behavior; orexin; sleep/wake regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Arousal / physiology*
  • Energy Metabolism / physiology*
  • Humans
  • Hypothalamic Area, Lateral / physiology*
  • Hypothalamic Area, Lateral / physiopathology*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Motivation / physiology*
  • Narcolepsy / physiopathology*
  • Neuropeptides / physiology*
  • Orexins


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins