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

RATIONALE: Prenatal exposure to infection is a risk factor for neuropsychiatric disorders that often co-occur with alcohol misuse. However, the mechanisms by which early exposure to infection might increase the risk of such disorders remains unclear. One hypothesis is that prenatal stressors interact with adolescent stressors (i.e., "two-hits") to promote alcohol misuse development.

OBJECTIVES: The current project tested whether maternal immune activation (MIA) combined with adolescent alcohol exposure (AA) increases the motivation to work for alcohol and negative affect in adulthood, and whether prenatal antioxidant treatment prevents these effects.

METHODS: Pregnant Sprague-Dawley rats were exposed to poly(I: C) (4 mg/kg) or saline on gestational day 15, and the antioxidant n-acetylcysteine (NAC; 100 mg/kg) or saline 24 h before and after poly(I: C). Offspring had 24-hour access to 10% ethanol and water during adolescence. In adulthood, offspring were trained to self-administer 10% ethanol and tested on escalating schedules of reinforcement. Elevated plus maze (EPM) behavior was assessed on non-self-administration days.

RESULTS: Poly(I: C) and NAC treatment independently led to an increased willingness to work for alcohol in males, but not females, relative to same-sex controls. NAC treatment suppressed the MIA-induced increase in alcohol-seeking. Poly(I: C) increased locomotor activity in the EPM in both sexes, independent of NAC, without altering open or closed arm time.

CONCLUSIONS: These data support the hypothesis that MIA-induced oxidative stress negatively influences development, leaving the brain more susceptible to the negative effects of AA, and increasing the risk of alcohol misuse in adulthood, particularly in males.