Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. This study demonstrates that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated low-dose glucocorticoid injections mimic these anti-depressive effects. Both repeated short-term stress and glucocorticoid injections activate neurons in overlapping brain regions and reverse stress-induced gene expression. Chemogenetic inhibition of specific prefrontal cortex neuronal projections also shows anti-depressive effects, suggesting a complex interplay of neural pathways in mediating the response to stress.

Eun-Hwa Lee, Jin-Young Park, Hye-Jin Kwon, Pyung-Lim Han