T.Jordan Walter, Ryan P. Vetreno, Fulton T. Crews
Cycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system – the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol on the corticosterone, endotoxin, microglial and neuronal response to acute stress.
Male Wistar rats were treated intragastrically with acute ethanol and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent ethanol and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD11b and neuronal activation marker c-Fos were performed.
Acute ethanol and acute stress interacted to increase plasma endotoxin and microglial CD11b, but not plasma corticosterone or neuronal c-Fos. Chronic ethanol caused a lasting sensitization of stress-induced plasma endotoxin, but not plasma corticosterone. Chronic ethanol also caused a lasting sensitization of stress-induced microglial CD11b, but not neuronal c-Fos.
These results find acute ethanol combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic ethanol followed by acute stress also increased plasma endotoxin and microglial CD11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.