Chronic Restraint Stress (CRS)

Chronic restraint stress is an experimental paradigm in which mice are physically restrained repeatedly over a period of weeks to model sustained psychological stress. Successful induction is confirmed behaviorally, by reduced sucrose preference (anhedonia) and increased immobility in the tail suspension and forced swim tests, and biochemically, by raised plasma cortisol and norepinephrine.

These readouts reflect the two main arms of the stress response, activation of the hypothalamic-pituitary-adrenal axis and of the sympathetic nervous system, which produce persistent elevations of glucocorticoids and catecholamines capable of reshaping the tumor microenvironment and attenuating antitumor immunity. Stress responses, HPA-axis activity, immune regulation and gut microbiome composition all differ between sexes, so findings from single-sex CRS studies are not automatically generalizable.