Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness states

PLoS One. 2013 Apr 19;8(4):e62391. doi: 10.1371/journal.pone.0062391. Print 2013.


Both orexin and neurotensin are expressed in the lateral hypothalamic area (LHA) and have been implicated in the regulation of feeding, motor activity and the reward system. A double label immunofluorescence and in situ hybridization studies showed that neurotensin colocalizes with orexin in neurons of the LHA. Pharmacological studies suggested that neurotensin excites orexin-producing neurons (orexin neurons) through activation of neurotensin receptor-2 (NTSR-2) and non-selective cation channels. In situ hybridization study showed that most orexin neurons express neurotensin receptor-2 mRNA but not neurotensin receptor-1 (Ntsr-1) mRNA. Immunohistochemical studies showed that neurotensin-immunoreactive fibers make appositions to orexin neurons. A neurotensin receptor antagonist decreased Fos expression in orexin neurons and wakefulness time in wild type mice when administered intraperitoneally. However, the antagonist did not evoke any effect on these parameters in orexin neuron-ablated mice. These observations suggest the importance of neurotensin in maintaining activity of orexin neurons. The evidence presented here expands our understanding of the regulatory mechanism of orexin neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hypothalamus / cytology*
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ion Channel Gating
  • Ion Channels / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Neurotensin / antagonists & inhibitors
  • Neurotensin / metabolism*
  • Orexins
  • Pyrazoles / pharmacology
  • Quinolines / pharmacology
  • Receptors, Neurotensin / metabolism
  • Sleep* / drug effects
  • Wakefulness* / drug effects


  • Intracellular Signaling Peptides and Proteins
  • Ion Channels
  • Neuropeptides
  • Ntsr2 protein, mouse
  • Orexins
  • Pyrazoles
  • Quinolines
  • Receptors, Neurotensin
  • SR 142948
  • Neurotensin

Grants and funding

This study was supported by the Government of Japan through its “Funding Program for Next Generation World-Leading Researchers”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.