Hypophysiotropic neurons of the paraventricular nucleus respond in spatially, temporally, and phenotypically differentiated manners to acute vs. repeated restraint stress: rapid publication

J Comp Neurol. 2002 Apr 15;445(4):293-307. doi: 10.1002/cne.10178.


Hypothalamic-pituitary-adrenal (HPA) responses to stress are initiated by parvicellular neurosecretory neurons in the medial parvicellular (mp) part of the paraventricular hypothalamic nucleus (PVH), which express corticotropin-releasing factor (CRF), among other neuropeptides. We have used an approach guided by patterns of stress-induced Fos expression to explore the manner in which anatomically and phenotypically defined components of the mpPVH respond to acute vs. repeated restraint stress. Hormonal indices of HPA activation in animals exposed to the last of 14 daily repeated restraint sessions were significantly lower than those in rats receiving a single restraint episode. Although this habituation was paralleled by global decrements in activation patterns across all PVH compartments, clear spatial-temporal differences in recruitment profiles were noted between dorsal and ventral aspects of the mpPVH. Thus, acute restraint provoked a biphasic Fos induction, which occurred first within the mpPVH and in an adjoining population of somatostatinergic cells in the periventricular region and only later within other aspects of the PVH. By contrast, Fos responses of habituated animals were monophasic and focused decisively within a discrete ventral aspect of the mpPVH. The ventral population was identified as comprising neurons that express CRF and/or enkephalin and, to a lesser extent, growth hormone-releasing factor. These results indicate a lack of homogeneity among stress-responsive parvicellular neurosecretory neurons and suggest that distinct complements of CRF cells may be preferentially involved in initiating HPA responses to acute stress and sustaining them in the repeated condition.

Publication types

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

MeSH terms

  • Acute Disease
  • Adrenocorticotropic Hormone / blood
  • Animals
  • Chronic Disease
  • Corticotropin-Releasing Hormone / genetics*
  • Habituation, Psychophysiologic / physiology
  • Hypothalamo-Hypophyseal System / cytology
  • Hypothalamo-Hypophyseal System / metabolism*
  • Immunohistochemistry
  • Male
  • Neural Pathways / physiology
  • Neurons / cytology
  • Neurons / metabolism*
  • Neuropeptides / genetics
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Long-Evans
  • Restraint, Physical
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology
  • Time Factors


  • Neuropeptides
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone