Urocortinergic neurons respond in a differentiated manner to various acute stressors in the Edinger-Westphal nucleus in the rat

J Comp Neurol. 2004 Dec 6;480(2):170-9. doi: 10.1002/cne.20343.


Corticotropin-releasing factor (CRF) was implicated as being a major contributor to the neurochemically mediated central regulation of stress response; however, an increasing body of evidence suggests that, besides CRF, other members of this neuropeptide family, such as urocortin (Ucn), may also play a role in modifying the efferent components of immune, endocrine, and behavioral responses to stress. Ucn's distribution in the rat brain has been demonstrated, with the most abundant Ucn-immunoreactive perikarya present in the Edinger-Westphal nucleus (E-WN). Acute pain and immobilization stresses recruit E-WN neurons, however, the activation pattern of E-WN Ucn neurons in response to various acute systemic and neurogenic challenges has not been compared in a single study. We therefore combined quantitative Fos imaging as a marker for neuronal activation with urocortin immunohistochemistry to visualize neurons induced by intravenous lipopolysaccharide (LPS; 100 microg/kg), ether inhalation, restraint, hyperosmotic (1.5 M NaCl i.p.), and hypotensive hemorrhage challenges. Neurons in the E-WN responded with the strongest Fos induction to LPS, but ether and restraint stress also resulted in massive Fos immunoreactivity 2 hours after stress. Unexpectedly, hyperosmotic and hypotensive hemorrhage stresses did not induce urocortinergic perikarya in this brain area 2 hours poststress. This challenge-specific recruitment of E-WN neurons was independent of stress-induced adrenal response. The biological significance and the stress-specific activation of E-WN urocortinergic neurons will be discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Corticotropin-Releasing Hormone / analysis
  • Corticotropin-Releasing Hormone / biosynthesis*
  • Male
  • Nerve Net / chemistry
  • Nerve Net / metabolism
  • Neurons / chemistry
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Stress, Physiological / metabolism*
  • Urocortins


  • Urocortins
  • Corticotropin-Releasing Hormone