Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation

Neuroscience. 1999;94(4):1183-8. doi: 10.1016/s0306-4522(99)00319-x.


These experiments examined the role of substance P-selective neurokinin 1 receptors in the restraint-induced activation of the rat locus coeruleus. Immunohistochemistry revealed high levels of neurokinin 1 receptor expression in the plasma membrane of tyrosine hydroxylase-positive locus coeruleus neurons. The selective neurokinin 1 receptor antagonists, RP 67580 (5 nmol) and L-760,735 (3.4 nmol), were administered intracerebroventricularly prior to restraint stress, and c-fos protein was measured as an index of locus coeruleus activation. Both antagonists attenuated the restraint-induced increase in locus coeruleus c-fos expression, whereas their inactive enantiomers were ineffective. These results suggest that neurokinin 1 receptors may mediate activation of locus coeruleus neurons during stress. Neurokinin 1 receptor antagonists may prove to be novel therapeutic compounds in the treatment of anxiety and depression.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Immunohistochemistry
  • Indoles / pharmacology
  • Injections, Intraventricular
  • Isoindoles
  • Locus Coeruleus / metabolism*
  • Male
  • Morpholines / pharmacology
  • Neurokinin-1 Receptor Antagonists
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-1 / physiology*
  • Restraint, Physical
  • Stress, Physiological / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism


  • Indoles
  • Isoindoles
  • L 760735
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, Neurokinin-1
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Tyrosine 3-Monooxygenase