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

Abstract

As key regulators of brain homeostasis, microglia and brain macrophages are vital to development. However, early life stress (ELS) experiences, like bullying, can have lasting consequences on microglial function. During ELS, microglia and brain macrophages alter their engagement with cells and synapses. These alterations can result in lasting adaptations in circuit function that could lead to an increased risk to develop maladaptive drinking behaviors and alcohol use disorder (AUD) in adulthood. Whether microglia and brain macrophages truly mediate the relationship between ELS and AUD remains elusive. Here, we report: 1) a novel early life psychosocial stress exposure, PSS, increases binge-like ethanol consumption in early adulthood. 2) This increase in ethanol drinking is associated with alterations in microglia and brain macrophage populations in the ventral hippocampus and across other brain regions. 3) Inhibiting microglia and brain macrophages using a CSF1-r inhibitor, GW2580, results in a trend towards a reduction in binge-like ethanol consumption and normalizes microglia and brain macrophage populations. Therefore, our study suggests that acutely inhibiting microglia and brain macrophage function during periods of early life psychosocial stress may help reduce the risk to develop risky drinking behaviors and AUD.HighlightsAn early life psychosocial stress (PSS) exposure increases ethanol consumptionPSS and ethanol consumption alter microglia function in the ventral hippocampusPSS and ethanol consumption have further consequences in other brain regionsMicroglial inhibition during PSS trends towards reducing ethanol consumptionMicroglial inhibition prevents microglia population changes in some brain regions