Repeated short-term (2h×14d) emotional stress induces lasting depression-like behavior in mice

Abstract

Chronic behavioral stress is a risk factor for depression. To understand chronic stress eff ects and the mechanism underlying stressinduced emotional changes, various animals model have been developed. We recently reported that mice treated with restraints for 2 h daily for 14 consecutive days (2h-14d or 2h×14d) show lasting depression-like behavior. Restraint provokes emotional stress in the body, but the nature of stress induced by restraints is presumably more complex than emotional stress. So a question remains unsolved whether a similar procedure with “emotional” stress is suffi cient to cause depression-like behavior. To address this, we examined whether “emotional” constraints in mice treated for 2h×14d by enforcing them to individually stand on a small stepping platform placed in a water bucket with a quarter full of water, and the stress evoked by this procedure was termed “waterbucket stress”. Th e water-bucket stress activated the hypothalamus-pituitary-adrenal gland (HPA) system in a manner similar to restraint as evidenced by elevation of serum glucocorticoids. Aft er the 2h×14d water-bucket stress, mice showed behavioral changes that were attributed to depression-like behavior, which was stably detected >3 weeks after last water-bucket stress endorsement. Administration of the anti-depressant, imipramine, for 20 days from time aft er the last emotional constraint completely reversed the stress-induced depression-like behavior. Th ese results suggest that emotional stress evokes for 2h×14d in mice stably induces depression-like behavior in mice, as does the 2h×14d restraint.