Acute exposure of rats to a severe stressor alters the circadian pattern of corticosterone and sensitizes to a novel stressor: Relationship to pre-stress individual differences in resting corticosterone levels

Horm Behav. 2020 Nov:126:104865. doi: 10.1016/j.yhbeh.2020.104865. Epub 2020 Oct 6.

Abstract

Traumatic events have been proposed to be associated with hypo-activity of the hypothalamic-pituitary-adrenal (HPA) axis, but data in animal models exposed to severe stressors are controversial and have important methodological concerns. Individual differences in resting or stress levels of corticosterone might explain some of the inconsistencies. We then studied this issue in male rats exposed to 2 h immobilization on boards (IMO), a severe stressor. Thirty-six rats were blood sampled under resting conditions four times a day on three non-consecutive days. Then, they were assigned to control (n = 14) or IMO (n = 22) to study the HPA response to IMO, the stressor-induced alterations in the circadian pattern of corticosterone (CPCORT), and the behavioral and HPA responsiveness to an open-field. Individual differences in pre-IMO resting corticosterone were inconsistent, but averaging data markedly improved consistency. The CPCORT was markedly altered on day 1 post-IMO (higher trough and lower peak levels), less altered on day 3 and apparently normal on day 7. Importantly, when rats were classified in low and high resting corticosterone groups (LCORT and HCORT, respectively), on the basis of the area under the curve (AUC) of the averaged pre-IMO data, AUC differences between LCORT and HCORT groups were maintained in controls but disappeared in IMO rats during the post-IMO week. Open-field hypo-activity and corticosterone sensitization were similar in LCORT and HCORT groups nine days after IMO. A single IMO exposure causes long-lasting HPA alterations, some of them dependent on pre-stress resting corticosterone levels, with no evidence for post-IMO resting corticosterone hypo-activity.

Keywords: Aggregated data; Circadian rhythm; Hypercorticosteronemia; Hypocorticosteronemia; Hypothalamic-pituitary-adrenal axis; Immobilization stress; Individual differences; PTSD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Circadian Rhythm / physiology
  • Conditioning, Classical / physiology
  • Corticosterone / blood
  • Corticosterone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Individuality
  • Male
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rest / physiology
  • Rest / psychology
  • Restraint, Physical / physiology
  • Restraint, Physical / psychology*
  • Stress Disorders, Post-Traumatic / blood
  • Stress Disorders, Post-Traumatic / etiology
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / blood
  • Stress, Psychological / metabolism*

Substances

  • Adrenocorticotropic Hormone
  • Corticosterone