Differential expression of orexin receptors 1 and 2 in the rat brain

J Comp Neurol. 2001 Jun 18;435(1):6-25. doi: 10.1002/cne.1190.


Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin-containing neurons have widespread projections and have been implicated in complex physiological functions including feeding behavior, sleep states, neuroendocrine function, and autonomic control. Two orexin receptors (OX(1)R and OX(2)R) have been identified, with distinct expression patterns throughout the brain, but a systematic examination of orexin receptor expression in the brain has not appeared. We used in situ hybridization histochemistry to examine the patterns of expression of mRNA for both orexin receptors throughout the brain. OX(1)R mRNA was observed in many brain regions including the prefrontal and infralimbic cortex, hippocampus, paraventricular thalamic nucleus, ventromedial hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. OX(2)R mRNA was prominent in a complementary distribution including the cerebral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nuclei, and many hypothalamic nuclei including the tuberomammillary nucleus, dorsomedial nucleus, paraventricular nucleus, and ventral premammillary nucleus. The differential distribution of orexin receptors is consistent with the proposed multifaceted roles of orexin in regulating homeostasis and may explain the unique role of the OX(2)R receptor in regulating sleep state stability.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autonomic Nervous System / physiology
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / physiology
  • Feeding Behavior / physiology
  • Gene Expression / physiology
  • Hippocampus / chemistry
  • Hippocampus / physiology
  • Hypothalamic Area, Lateral / chemistry
  • Hypothalamic Area, Lateral / physiology*
  • In Situ Hybridization
  • Locus Coeruleus / chemistry
  • Locus Coeruleus / physiology
  • Male
  • Midline Thalamic Nuclei / chemistry
  • Midline Thalamic Nuclei / physiology
  • Narcolepsy / physiopathology
  • Orexin Receptors
  • RNA, Messenger / analysis
  • Raphe Nuclei / chemistry
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Sprague-Dawley / physiology*
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / genetics*
  • Sleep / physiology
  • Specific Pathogen-Free Organisms
  • Ventromedial Hypothalamic Nucleus / chemistry
  • Ventromedial Hypothalamic Nucleus / physiology


  • Orexin Receptors
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide