Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal

Trends Pharmacol Sci. 2011 Aug;32(8):451-62. doi: 10.1016/ Epub 2011 May 11.


Avoiding danger and finding food, which are life-sustaining activities that are regulated by emotion, reward and energy balance, require proper wakefulness. The orexin system controls sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis. Recent findings have brought about the possibility of novel therapies targeting the orexin system for sleep disorders, including insomnia and narcolepsy-cataplexy, as well as other pathological conditions such as obesity and drug addiction [1]. In this review, we will discuss the current understanding of the integrative physiology and clinical perspectives of the orexin system. We will briefly review signaling through orexin A and B receptors and discuss the role of orexins in the pathophysiology of narcolepsy. We will also examine connections between orexin neurons and other brain areas involved in feeding behavior, reward and emotion. Finally, we will consider the therapeutic potential of drugs that target orexin receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / physiology*
  • Brain Mapping
  • Dogs
  • Emotions
  • Energy Metabolism / physiology
  • Feeding Behavior / physiology
  • Homeostasis / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Models, Neurological
  • Narcolepsy / physiopathology
  • Neurons / metabolism*
  • Neuropeptides / chemistry
  • Neuropeptides / metabolism*
  • Orexin Receptors
  • Orexins
  • Rats
  • Receptors, G-Protein-Coupled* / antagonists & inhibitors
  • Receptors, G-Protein-Coupled* / metabolism
  • Receptors, Neuropeptide* / antagonists & inhibitors
  • Receptors, Neuropeptide* / metabolism
  • Reward
  • Signal Transduction / physiology
  • Sleep Wake Disorders
  • Wakefulness / physiology


  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide