Innate immune stimulation prevents chronic stress-induced depressive and anxiogenic-like behaviors in female mice.

It has been reported that pre-stimulation of the innate immune system can prevent depressive and anxiogenic-like behaviors in chronically stressed male mice. However, it is unclear whether similar effects can be observed in female animals. In the present study, we investigated this question in female mice. Our results showed that a single injection of lipopolysaccharide (LPS; 100 μg/kg) one day before stress exposure prevented increased immobility time in the tail suspension test and forced swimming test and decreased sucrose intake in the sucrose preference test in chronic unpredictable stress (CUS)-treated female mice. The single LPS pre-injection (100 μg/kg) prevented the CUS-induced decrease in (i) time spent in open arms and number of entries into open arms in the elevated plus maze test, (ii) time spent in lit side in the light-dark test, and (iii) time spent in the central region of the open field in the open field test, along with no changes in locomotor activity. It was also found that the single LPS pre-injection in female mice prevented the CUS-induced increase in the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA in the hippocampus and medial prefrontal cortex. Inhibition of innate immune system stimulation by minocycline pretreatment abrogated the preventive effect of LPS on CUS-induced depressive and anxiogenic-like behaviors and neuroinflammatory responses in the hippocampus and medial prefrontal cortex in female mice. These results suggest that pre-stimulation of the innate immune system by LPS injection may prevent the development of behavioral abnormalities in female mice.