135. Re-exposure to social defeat initiated anxiogenic macrophage recruitment into the brain of sensitized mice

Abstract

Repeated social defeat (RSD) is a murine stressor that promotes immune and behavioral consequences observed in humans exposed to psychosocial stress. Previous results show that RSD increased the inflammatory profile of brain CD11b + cells and caused prolonged anxiety-like behavior. The objective of this study was to determine the neuroinflammatory profile of brain CD11b + cells associated with prolonged anxiety-like behavior after RSD. Exposure to RSD increased circulating monocytes, promoted macrophage trafficking in the brain, and caused anxiety-like behavior that was evident 8 days after stress cessation. Moreover, RSD promoted social avoidance that persisted 24 days after stress cessation. Because stress-induced alterations were diminished after 24 days, the extent to which RSD sensitized stress responses was determined. Mice were sensitized (RSD) and then re-exposed to social defeat (1 cycle) 24 days later. Re-exposure to social defeat significantly increased recruitment of macrophages in the brain and re-established anxiety-like behavior in sensitized mice. This is relevant because none of these responses were observed in naïve mice exposed to one cycle of social defeat. These results show that while RSD-induced immune and behavioral responses returned to baseline 24 days after stress cessation, RSD exposure sensitized mice to stressor re-exposure. Taken together, these findings implicate macrophage recruitment into the brain as a key intermediate in stress-induced anxiety disorders and demonstrate that neuro-immune pathways are sensitized to initiate immunological and behavioral responses.