A study from Washington State University has found that exposure to infection and other immune stress during pregnancy can increase the risk of alcohol misuse in adulthood. The research, published in the journal Psychopharmacology, also suggests that prenatal antioxidant treatment may help reduce this risk.
The study addresses how early biological stress can shape addictive behaviors later in life. It builds on previous knowledge that prenatal factors such as infection, diet, and stress can influence lifelong health outcomes. Although links between prenatal infection and neuropsychiatric disorders associated with alcohol misuse are established, the mechanisms behind these associations are not fully understood.
"What we don't understand is how that changes the brain to make someone more susceptible to mental illness or substance abuse disorder," said Henricks, a lead researcher on the project. "We know it's a risk factor, but we don't know how it works very well."
The research team studied maternal immune activation by exposing pregnant rats to a synthetic substance simulating viral infection. Some of these rats were treated with the antioxidant N-acetylcysteine (NAC) before and after immune activation, while control animals received saline.
The offspring who experienced prenatal immune stress were more likely to self-administer alcohol as adults if they had also been exposed to alcohol during adolescence. This finding supports a "two-hit" model for addiction risk: early immune stress interacts with later experiences to increase the likelihood of developing an alcohol use disorder.
However, when mothers received antioxidant treatment during pregnancy, this response was suppressed in their offspring. According to Henricks, "This suggests that oxidative stress is significantly contributing to why prenatal infection might be a risk factor." The results indicate NAC could be explored as a potential treatment for reducing the risk of alcohol misuse in humans.
The study also found differences based on sex. Male offspring were more affected by prenatal infection and showed clearer responses to antioxidant treatment compared to females, who did not exhibit increased alcohol-seeking behavior. This highlights the importance of considering biological sex in addiction research and prevention efforts.
Henricks' Brain Alcohol Research Lab team contributed to the paper: PhD student Skylar E. Nicholson (lead author), PhD student Kelly A. Hewitt, and undergraduate Cara S. Brauen.
Henricks is continuing research into prenatal immune stress effects, including studies related to cannabis use and investigations into how oxidative stress influences brain function. She noted: "One thing we think oxidative stress is doing to the brain is impacting synaptic plasticity, which is essentially the ability of your neurons to make connections with one another."
Excessive drinking leads to about 178,000 deaths annually in the United States and costs $249 billion each year due to lost productivity and healthcare expenses according to data from the U.S. Centers for Disease Control (https://www.cdc.gov/alcohol/features/excessive-drinking.html).
