Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior. Two independent sets of control (CON), CRST, and CRST+RS5 groups were prepared. Mice were subjected to CRST treatment followed by RS5, and then sacrificed on post-stress day 22. Total RNA was extracted from the pooled PL tissue of 6 – 7 animals in each group. RNA extraction and hybridization on Illumina microarrays.