Sympathetic nervous system contributes to enhanced corticosterone levels following chronic stress

Psychoneuroendocrinology. 2016 Jun;68:163-70. doi: 10.1016/j.psyneuen.2016.02.027. Epub 2016 Feb 26.


Exposure to chronic stress often elevates basal circulating glucocorticoids during the circadian nadir and leads to exaggerated glucocorticoid production following exposure to subsequent stressors. While glucocorticoid production is primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis, there is evidence that the sympathetic nervous system can affect diurnal glucocorticoid production by direct actions at the adrenal gland. Experiments here were designed to examine the role of the HPA and sympathetic nervous system in enhancing corticosterone production following chronic stress. Rats were exposed to a four-day stress paradigm or control conditions then exposed to acute restraint stress on the fifth day to examine corticosterone and ACTH responses. Repeated stressor exposure resulted in a small increase in corticosterone, but not ACTH, during the circadian nadir, and also resulted in exaggerated corticosterone production 5, 10, and 20min following restraint stress. While circulating ACTH levels increased after 5min of restraint, levels were not greater in chronic stress animals compared to controls until following 20min. Administration of astressin (a CRH antagonist) prior to restraint stress significantly reduced ACTH responses but did not prevent the sensitized corticosterone response in chronic stress animals. In contrast, administration of chlorisondamine (a ganglionic blocker) returned basal corticosterone levels in chronic stress animals to normal levels and reduced early corticosterone production following restraint (up to 10min) but did not block the exaggerated corticosterone response in chronic stress animals at 20min. These data indicate that increased sympathetic nervous system tone contributes to elevated basal and rapid glucocorticoid production following chronic stress, but HPA responses likely mediate peak corticosterone responses to stressors of longer duration.

Keywords: ACTH; CRH; Corticosterone; Ganglionic blocker; HPA axis.

Publication types

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

MeSH terms

  • Adrenal Glands / metabolism
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Circadian Rhythm / physiology
  • Corticosterone / blood
  • Corticosterone / metabolism*
  • Glucocorticoids / metabolism
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptors, Glucocorticoid / metabolism
  • Stress, Physiological / physiology*
  • Stress, Psychological / blood
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Sympathetic Nervous System / metabolism*


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Adrenocorticotropic Hormone
  • Corticosterone