Behavioural brain researchDec 18, 2025

Chronic stress may change how dexamethasone affects stress-related gene activity in mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

Chronic social defeat stress (CSDS) results in significant dysregulation of HPA axis-related genes in C57Bl/6 mice.

CSDS led to decreased expression of genes such as Crh and Crhbp in the hypothalamus and Mc2r and Nr3c1 in the adrenal glands.
An increase in the expression of steroidogenic enzymes Cyp11a1 and Cyp11b1 was observed, which may contribute to higher corticosterone levels.
The response to dexamethasone was altered following CSDS, suggesting a delayed recovery of glucocorticoid receptor signaling.
Findings indicate potential glucocorticoid resistance associated with chronic social stress in these mice.

Simplified

Chronic social stress is a major risk for psychopathologies such as depression, often leading to altered hypothalamic-pituitary-adrenal (HPA) axis function and glucocorticoid resistance. This study examines how chronic social defeat stress (CSDS) affects sensitivity to dexamethasone by analyzing HPA axis genes expression in C57Bl/6 mice. Adult male mice were subjected to 30 days of stress, followed by dexamethasone or saline administration. Genes expression was analyzed in the hypothalamus, prefrontal cortex (PFC; Nr3c1 only), and adrenal glands at multiple time points post-treatment. CSDS induced marked dysregulation of HPA axis-related genes, including a decrease in hypothalamic Crh and Crhbp, and adrenal Mc2r, Nr3c1, alongside an upregulation of steroidogenic enzymes Cyp11a1 and Cyp11b1, which may account for the elevated corticosterone levels observed under chronic stress conditions. CSDS alters the genes expression response to dexamethasone, indicating a delayed recovery of glucocorticoid receptor signaling in the brain and adrenal glands. Our findings reveal significant stress-induced alterations in the expression of key HPA axis genes, suggesting impaired glucocorticoid receptor signaling and potential glucocorticoid resistance in stressed mice.

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Chronic stress may change how dexamethasone affects stress-related gene activity in mice

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