Prenatal anti-oxidant treatment suppresses maternal immune activation induced increases in alcohol self-administration in a sex-specific manner

Prenatal exposure to infection is a risk factor in the development of several neuropsychiatric disorders, including schizophrenia and depression, which often co-occur with alcohol misuse, exacerbating adverse outcomes. Despite these consequences, little is understood regarding the mechanisms by which early exposure to infection might increase the risk of alcohol misuse. We have previously demonstrated that maternal immune activation (MIA) combined with adolescent alcohol exposure (AA) increases home-cage drinking and disrupts neural circuit function in adulthood. The current project aims to determine whether these findings extend to the motivation to work for alcohol, and whether prenatal anti-oxidant treatment can prevent the effects of MIA on self-administration. Pregnant Sprague-Dawley rats were exposed to poly(I:C) (4mg/kg) or saline on gestational day 15, and the anti-oxidant n-acetylcysteine (NAC; 100 mg/kg) or saline 24 hours before and after MIA. Offspring were given 24-hour home cage access to 10% ethanol and water dur adolescence. In adulthood, offspring were trained to self-administer 10% ethanol and tested on escalating schedules of reinforcement: fixed ratio (FR)1, FR2, FR4, and progressive ratios (PR). MIA and NAC independently led to an increased willingness to work for alcohol in males, compared to saline-treated rats. NAC treatment suppressed the effect of MIA on self-administration behavior. These data support the hypothesis that oxidative stress caused by MIA negatively influences development, priming the brain to be more susceptible to the negative effects of AA, leading to an increased risk of alcohol misuse in adulthood, particularly in males.