Stress-linked drinking in youth tied to lasting brain changes in mice

Drinking heavily to cope with stress in early adulthood may leave lasting effects on brain circuits involved in decision-making, according to University of Massachusetts Amherst researchers. The work matters because the team found changes in mice that persisted into middle age after long periods without alcohol and were linked to a higher risk of returning to drinking under stress.

The study, published in Alcohol, Clinical and Experimental Research, examined how chronic alcohol exposure and stress interact over time. UMass Amherst said the findings could help shape treatments that address long-term brain changes tied to alcohol use, rather than focusing only on stopping drinking.

Elena Vazey, an associate professor of biology at UMass Amherst and senior author of the study, said her lab studies the brain circuits behind decision-making. She said the researchers wanted to understand how drinking in early adulthood, when paired with stress, affects those circuits as animals age.

Stress and alcohol showed a combined effect

The researchers studied mice with support from the National Institute on Alcohol Abuse and Alcoholism. UMass Amherst said mice were used because many of their brain circuits resemble those found in humans.

The team reported that alcohol and stress together produced stronger effects than either factor alone. Mice exposed to heavy drinking in the setting of chronic stress during early adulthood were more likely to drink again when stressed in middle age, even after extended abstinence, according to the university.

The researchers found little difference in general learning between middle-aged mice with a history of stress-related heavy drinking and mice with lighter drinking histories. The clearer deficit involved cognitive flexibility: the ability to adjust behavior when circumstances change.

Vazey said middle age is a period when problems can accumulate. She said alcohol is a known risk factor for early cognitive decline, and the team saw trouble adapting to changing situations that resembles problems seen in the early stages of dementia.

Brainstem region showed persistent damage

To look for a mechanism, the researchers focused on the locus coeruleus, a small region in the brainstem involved in adaptive decision-making in mice and humans. In healthy brains, UMass Amherst said, the region becomes active during stress and then settles back down afterward.

In mice exposed to both chronic stress and alcohol, the locus coeruleus lost molecular machinery that helps it shut itself off, according to the researchers. The team said that disruption appeared to weaken the region’s role in guiding decisions.

The study also found elevated oxidative stress in the locus coeruleus. UMass Amherst described oxidative stress as a form of cellular damage seen in the brains of people with Alzheimer’s disease and capable of harming cells throughout the body.

Even after prolonged abstinence, the middle-aged mice with earlier heavy drinking and stress showed little evidence that this damage had repaired, according to the university. Vazey said the damage may help explain why some animals returned to alcohol after abstinence and why decision-making remained impaired.

The journal reference lists the paper as “Impact of chronic alcohol and stress on midlife cognition and locus coeruleus integrity in mice,” by O. Revka and colleagues. UMass Amherst said the findings point to persistent brain differences that treatment strategies may need to address after a history of chronic stress and drinking.

This story draws on original reporting from ScienceDaily.