Microglial activation in the anterior cingulate cortex: A biological marker of early adverse events and future vulnerability to develop alcohol use disorder

Epidemiological studies have long acknowledged that only a minority of the population is at risk of losing control over alcohol consumption. Aiming at identifying the roots of this vulnerability, ongoing evidence from our laboratory revealed a significant vulnerability to lose control over alcohol consumption in male Wistar rats subjected to a chronic mild unpredictable stress (CMUS) during adolescence. This excessive alcohol seeking behaviour correlated with significant changes in the gut microbiota composition. Most importantly, Fecal Microbiota Transplantation (FMT) from resilient to vulnerable rats not only effectively changed the gut-microbiota composition of receivers, but it also alleviated symptoms of addiction-like behaviours and reduced signs of peripheral inflammation. The present study aims at confirming the effectiveness of FMT to reduce central inflammation as well. Extensive morphological and skeletal analyses converged to identifying an amoeboid shape of the microglia in the Anterior Cingulate Cortex (ACC), but not in the Prelimbic (PRL), of stress rats in contrast to control animals. Current investigations aim at processing brain slices of stress rats post FMT, notably targeting the ACC, PRL and amygdala nuclei. To our knowledge, this is the first set of observations confirming that FMT represent an effective therapeutic strategy for reducing both signs of central/peripheral inflammation and addiction-like behaviour.