A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland

Int J Mol Sci. 2021 Dec 8;22(24):13235. doi: 10.3390/ijms222413235.


Background: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production.

Methods: Rats were exposed to PSS for ten days. Thirty days later, the rats' anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex.

Results: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats.

Conclusion: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.

Keywords: CPTSD; adrenal gland; behavior; glucocorticoids.

MeSH terms

  • Adrenal Glands / metabolism
  • Adrenal Glands / pathology
  • Adrenal Glands / physiopathology*
  • Animals
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Corticosterone / analogs & derivatives
  • Corticosterone / blood
  • Corticosterone / metabolism*
  • Desoxycorticosterone / blood
  • Desoxycorticosterone / metabolism
  • Disease Models, Animal
  • Phenotype
  • Rats
  • Stress Disorders, Post-Traumatic / etiology
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / pathology*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism
  • Zona Fasciculata / metabolism
  • Zona Fasciculata / pathology
  • Zona Fasciculata / physiopathology


  • Desoxycorticosterone
  • 11-dehydrocorticosterone
  • Corticosterone