Abstract
OBJECTIVE: Hypothalamic‒pituitary‒adrenal axis response is essential for coping with acute stressors, while maladaptive stress coping may increase the risk of major depressive disorder. We previously demonstrated that behavioral patterns induced by prior psychological stress predict coping levels in response to future stressors. This study investigated whether activating corticotropin-releasing hormone (CRH) and corticosteroid receptors mediates psychological stress-induced coping behavior. METHODS: Behavioral responses in mice exhibiting a fear response elicited by exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic component of fox feces, as preceding psychological stress, were assessed by measuring central zone entries in an open-field test. Time spent immobile during the tail suspension test was evaluated as a subsequent aversive stress-coping level. CRH overexpression was induced by adeno-associated virus injection (Hypo-CRH-OE) into the paraventricular hypothalamic nucleus. Dexamethasone (10 μg/kg, s.c.), a glucocorticoid receptor agonist, or fludrocortisone (5 mg/kg, s.c.), a mineralocorticoid receptor agonist was administered 30 min before behavioral tests. RESULTS: Hypo-CRH-OE mice exhibited significantly higher plasma corticosterone levels than controls, without changes in baseline of locomotor activity or innate fear sensitivity. During TMT exposure, Hypo-CRH-OE mice showed lower central activity in the open-field test, accompanied by longer immobility time in the tail suspension test (TST), disrupting the correlation between these behaviors. A similar disruptive effect was observed in fludrocortisone-treated mice but not in dexamethasone-treated mice. Additionally, fludrocortisone, but not dexamethasone, prolonged immobility during the TST. CONCLUSIONS: Preceding psychological stress-induced behavioral patterns may predict coping levels through mineralocorticoid receptor activations offering a potential target for improving stress resilience and preventing depression.