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

Abstract

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.

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

“…However, this decrease was significantly more pronounced in PSs than in PSr rats. This finding is consistent with our previous results showing that in low-anxiety rats with experimental PTSD/anxiety-like behavior, the reduction in the plasma CORT concentration was transient, while the high-anxiety rats demonstrated sustained CORT reduction [ 26 ]. Also, in other studies [ 63 ], PTSD-susceptible rats had decreased plasma concentrations of CORT as well as reduced corticotropin-releasing factor expression.…”

“…Psychological stress, anxiety, and PTSD share many common features [ 32 , 33 ]. In this study, we produced stress using the same methods as our previous studies [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Rats were exposed to repeated PS, and many rats developed anxiety-like behavior by day 14 of the post-stress period.…”

“…This model has been considered a relevant model of experimental PTSD [ 1 , 2 ], although we now see that only 45% of the rats exposed to PS can be said to develop experimental PTSD. In this study, we used a novel approach that had been used in our recent investigations [ 20 , 25 , 26 , 27 ]: rats exposed to PS were segregated into PS-resilient and PS-susceptible groups based on their normal or increased AI, respectively. This approach allowed us to identify and evaluate specific factors contributing to PS resilience or vulnerability.…”

“…A modified PS model was used, initially described by Cohen and Zohar [ 2 ] and as used in our prior studies [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. PS was induced by exposing rats to cat urine scent for 10 min daily for 10 days.…”

“…Our goal is to identify factors that could be implicated in the antistress protection of cerebral circulation and PS resilience. To achieve these goals, rats are first segregated into PSr and PSs groups, based on an anxiety index (AI) determined in an elevated plus maze test [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Then, basal CBF and endothelial function in these subgroups are compared.…”