Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia

Physiol Behav. 2005 Apr 13;84(5):697-706. doi: 10.1016/j.physbeh.2005.02.011. Epub 2005 Mar 23.


A bidirectional relationship exists between depression and cardiovascular disease. Patients with major depression are more likely to develop cardiac events, and patients with myocardial infarction and heart failure are more likely to develop depression. A feature common to both clinical syndromes is activation of proinflammatory cytokines and stress hormones, including the hypothalamic-pituitary-adrenal axis and the renin-angiotensin-aldosterone system. In the present study we examined the hypothesis that exposure to chronic mild stress (CMS), an experimental model of depression that induces anhedonia in rats, is sufficient to activate the production of proinflammatory cytokines and stress hormones that are detrimental to the heart and vascular system. Four weeks of exposure of male, Sprague-Dawley rats to mild unpredictable environmental stressors resulted in anhedonia which was operationally defined as a reduction in sucrose intake without a concomitant effect on water intake. Humoral assays indicated increased plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), plasma renin activity, aldosterone, and corticosterone in the CMS exposed rats. Tissue TNF-alpha and IL-1beta were increased in the hypothalamus, and TNF-alpha was increased in the pituitary gland. These humoral responses to CMS, associated with anhedonia as an index of depression in the rat, are likely to be associated with neurohumoral mechanisms that may contribute to adverse cardiac events. The findings provide a basis for examining more directly the interactions among the central, endocrine, and immune systems in depression associated with heart disease.

Publication types

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

MeSH terms

  • Aldosterone / blood
  • Animals
  • Body Weight / physiology
  • Brain Chemistry / physiology
  • Central Nervous System / physiopathology
  • Chronic Disease
  • Corticosterone / blood
  • Cytokines / blood
  • Cytokines / metabolism*
  • Food Preferences / physiology*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Immune System / physiopathology
  • Male
  • Neurosecretory Systems / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Renin / blood
  • Renin-Angiotensin System / physiology
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology*
  • Sucrose
  • Taste / drug effects


  • Cytokines
  • Aldosterone
  • Sucrose
  • Renin
  • Corticosterone