Increased corticotropin-releasing factor concentrations in the bed nucleus of the stria terminalis of anhedonic rats

Eur J Pharmacol. 2000 Jul 28;401(1):39-46. doi: 10.1016/s0014-2999(00)00412-x.

Abstract

Chronic mild stress in rats is an antidepressant-responsive model for anhedonic symptoms of major depression. Many patients with depression exhibit alterations in hypothalamic-pituitary-adrenal axis activity, and corticotropin-releasing factor (CRF) neuronal function. This study investigated the potential involvement of CRF and CRF receptors in the development of chronic mild stress-induced anhedonia in rats. Rats were subjected to 19 days of chronic mild stress, during which time anhedonia was periodically assessed by determining the threshold for self-stimulation of the ventral tegmental area. Anhedonic rats exhibited a 50% increase in CRF concentrations in the bed nucleus of the stria terminalis compared to control rats. There were no significant changes in hypothalamic-pituitary-adrenal axis activity, CRF or CRF(1) receptor mRNA expression, or CRF receptor binding in the brain regions analyzed. Though preliminary, these results are consistent with the hypothesis that chronic stress-induced modulation of CRF function in specific brain structures such as the bed nucleus of the stria terminalis may contribute to the pathophysiology of depression.

Publication types

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

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Behavior, Animal / physiology
  • Binding, Competitive
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism*
  • Depressive Disorder / physiopathology*
  • Gene Expression
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Septal Nuclei / metabolism*
  • Stress, Physiological / physiopathology

Substances

  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone