Intranasal lipopolysaccharide administration prevents chronic stress-induced depression- and anxiety-like behaviors in mice

We recently reported that intraperitoneal injection of a low dose of lipopolysaccharide (LPS) prevents chronic stress-induced depression-like behaviors in mice. In this study, we reported that a single intranasal LPS administration (10 μg/mouse) one day prior to stress exposure produced prophylactic effects on chronic social defeat stress (CSDS)-induced depression-like behaviors, which was indicated by the reduction in social interaction time in the social interaction test and the decrease in immobility time in the tail suspension test and forced swimming test. The single intranasal LPS administration prior to stress exposure was also found to prevent CSDS-induced anxiety-like behaviors, including prevention of CSDS-induced decrease in the time spent in open arms in the elevated plus maze test, decrease in the time spent in lit side in the light-dark test, and decrease in the time spent in central regions in the open field test, along with no changes in locomotor activity. Further analysis showed that the single intranasal LPS administration one day prior to stress exposure prevented CSDS-induced increase in levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA in the hippocampus and prefrontal cortex. Inhibition of innate immune stimulation by minocycline pretreatment not only abrogated the preventive effect of intranasal LPS administration on CSDS-induced depression- and anxiety-like behaviors, but also abrogated the preventive effect of intranasal LPS administration on CSDS-induced neuroinflammatory responses in the hippocampus and prefrontal cortex. These results demonstrate that intranasal administration of innate immune stimulants could be a potential approach for the prevention of depression and anxiety.