Hypocretin/orexin in arousal and stress

Brain Res. 2010 Feb 16:1314:91-102. doi: 10.1016/j.brainres.2009.09.019. Epub 2009 Sep 11.


Multiple lines of evidence indicate that hypocretin/orexin (HCRT) participates in the regulation of arousal and arousal-related process. For example, HCRT axons and receptors are found within a variety of arousal-related systems. Moreover, when administered centrally, HCRT exerts robust wake-promoting actions. Finally, a dysregulation of HCRT neurotransmission is associated with the sleep/arousal disorder, narcolepsy. Combined, these observations suggested that HCRT might be a key transmitter system in the regulation of waking. Nonetheless, subsequent evidence indicates that HCRT may not play a prominent role in the initiation of normal waking. Instead HCRT may participate in a variety of processes such as consolidation of waking and/or coupling metabolic state with behavioral state. Additionally, substantial evidence suggests a potential involvement of HCRT in high-arousal conditions, including stress. Thus, HCRT neurotransmission is closely linked to high-arousal conditions, including stress, and HCRT administration exerts a variety of stress-like physiological and behavioral effects that are superimposed on HCRT-induced increases in arousal. Combined, this evidence suggests the hypothesis that HCRT may participate in behavioral responding under high-arousal aversive conditions. Importantly, these actions of HCRT may not be limited to stress. Like stress, appetitive conditions are associated with elevated arousal levels and a stress-like activation of various physiological systems. These and other observations suggest that HCRT may, at least in part, exert affectively neutral actions that are important under high-arousal conditions associated with elevated motivation and/or need for action.

Publication types

  • Review

MeSH terms

  • Animals
  • Arousal / physiology*
  • Behavior, Animal / physiology
  • Brain / anatomy & histology
  • Brain / physiology*
  • Energy Metabolism / physiology
  • Fear / physiology
  • Humans
  • Hypothalamo-Hypophyseal System / anatomy & histology
  • Hypothalamo-Hypophyseal System / physiology
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Limbic System / anatomy & histology
  • Limbic System / physiology
  • Motivation / physiology
  • Neuropeptides / physiology*
  • Orexins
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology*


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins