Concurrent consumption of ethanol and corticosterone during adolescence alters neuroimmune sensitivity in Sprague...

Chronic stress and alcohol consumption influence various features of neuroimmune reactivity, including neurobehavioral outcomes, induction of neuroimmune genes, blood-brain barrier (BBB) permeability, and core body temperature regulation. The goal of the present studies was to characterize a novel model of chronic ethanol intake in which exogenous corticosterone (CORT), a principal end-product of the Hypothalamic-Pituitary-Adrenal (HPA) axis, was co-consumed in 10 % ethanol. In adolescence (P28-32), pair-housed Sprague-Dawley rats were given a single bottle containing 10 % ethanol with varying concentrations of CORT (0, 25, 50, or 100μg/mL) for 48 h, followed by 48 h of tap water. This four-day sequence was repeated for 12 cycles, ending in early adulthood (P76-80). In Experiment 1, following CORT and ethanol exposure, rats were challenged with restraint stress (30 min), and changes in neuroimmune gene expression were evaluated. Rats with a history of 10 % ethanol + 100μg/mL CORT showed increased interleukin (IL)-6 mRNA expression in the hippocampus relative to water comparators. Experiment 2 probed BBB permeability after perfusion with FITC-labeled dextran (20 kDa), and no changes were found. Remaining experiments evaluated the effects of ethanol/CORT drinking on ethanol-induced hypothermia (Experiment 3) and polyinosinic:polycytidylic acid (Poly I:C)-induced fever (Experiment 4). In females, ethanol consumption (regardless of CORT) delayed return to baseline following the hypothermic response, and in males, 25μg/mL CORT exclusively suppressed fever following Poly I:C challenge. Together, these findings validate a concurrent exposure model of intermittent CORT and ethanol which is translationally relevant to the adolescent experience, and uncovered ethanol- and CORT-induced changes in adult neuroimmune reactivity.