Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior

Brain Res. 2005 May 17;1044(1):116-21. doi: 10.1016/j.brainres.2005.03.002. Epub 2005 Apr 12.


Orexins (hypocretins) are neuropeptides expressed specifically in neurons in the lateral hypothalamic area and are known to be involved in the regulation of vigilance and feeding behavior. However, the relationship between orexin and emotional behaviors like anxiety is still poorly understood. Therefore, in this report we evaluated the effect of intracerebroventricular injection of orexin-A in two major anxiety tests, the light-dark exploration test (mouse) and the elevated plus-maze test (mouse, rat). Orexin increased time spent in the dark compartment in the light-dark test and time spent on the closed arms in the elevated plus-maze test. These results were not caused by a hypothetical sedative or activity-inducing effect of orexin-A because spontaneous locomotor activity did not alter upon orexin-A application under novel conditions. We therefore suggest an anxiogenic effect of orexin-A. To our knowledge, this is the first report about a relationship between orexin-A and anxiety.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Anxiety / etiology*
  • Anxiety / physiopathology
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Injections, Intraventricular / methods
  • Intracellular Signaling Peptides and Proteins / toxicity*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuropeptides / toxicity*
  • Orexins
  • Rats
  • Rats, Wistar
  • Time Factors


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins