Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density.

UNLABELLED: Early life stress (ELS) has lasting consequences on microglia and brain macrophage function. During ELS, microglia and brain macrophages alter their engagement with synapses leading to changes in neuronal excitability. Further, ELS can induce innate immune memory formation in microglia and brain macrophages resulting in altered responsivity to future environmental stimuli. These alterations can result in lasting adaptations in circuit function and may mediate the relationship between ELS and the risk to develop alcohol use disorder (AUD). Whether microglia and brain macrophages truly mediate this relationship remains elusive. Here, we report: 1) an ELS model, psychosocial stress (PSS), increases binge-like ethanol consumption in early adulthood. 2) Repeated binge-like ethanol consumption increases microglia and brain macrophage population densities across the brain. 3) PSS may elicit innate immune memory formation in microglia and brain macrophages leading to altered population densities following repeated binge-like ethanol consumption. 4) Microglia and brain macrophage inhibition trended towards preventing PSS-evoked changes in binge-like ethanol consumption and normalized microglia and brain macrophage population densities. Therefore, our study suggests that acutely inhibiting microglia and brain macrophage function during periods of early life PSS may prevent innate immune memory formation and assist in reducing the risk to develop AUD.

HIGHLIGHTS: An early life psychosocial stress (PSS) exposure increases ethanol consumptionMicroglial inhibition during PSS trends towards reducing ethanol consumptionBinge ethanol consumption increases microglial count and alters cell proximityEarly life PSS alters microglial responsivity to binge ethanol consumptionMicroglial inhibition may prevent microglial innate immune memory formation.