Health. Alcohol: Why does excessive consumption damage the brain?

New scientific findings, published today in Science Advances, provide a new explanation for the lasting effects of alcohol on cognition—the set of mental processes involved in acquiring, processing, remembering, and using information—since rats chronically exposed to high amounts of alcohol exhibited difficulty making decisions on a complex task, even after several months of withdrawal.

Why? Certain key areas of their brains had undergone major functional changes compared to healthy rats.

" We know that people with alcohol addiction have deficits in learning and decision-making, which can influence their choices related to their consumption ," explains Patricia Janak, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, USA, a researcher from the team that made this discovery. "We needed an animal model to better understand how chronic alcohol abuse alters the brain. Studying these decision-making difficulties in animals sheds light on what happens in humans ."

Thanks to this research, scientists now have a new model for studying the cognitive alterations observed in people suffering from alcohol use disorders.

What did the experiments consist of?

In these experiments, conducted by Yifeng Cheng, a researcher in Patricia Janak's lab, rats were exposed to very high doses of alcohol for a month. After a washout period of nearly three months, they were given a reward-based decision-making test alongside a control group of rats that had not consumed alcohol.

The test involved choosing between two levers to obtain a reward. One lever offered a higher probability of reward than the other. The rats quickly learned to favor the more advantageous lever, but the researchers complicated the task by periodically reversing the reward probability between the two levers.

To maximize their gains, the rats had to quickly adapt their strategy to changes. This task required memory and adaptability. However, the alcohol-exposed rats performed significantly worse.

Previous animal studies have not accurately reflected the rapid decision-making deficits observed in humans with alcoholism. This is likely due, the researchers say, to the rats being asked to perform tasks that were too simple until now.

" Our test was particularly demanding, and the alcohol-exposed rats didn't perform as well ," says Patricia Janak. Specifically, when the correct answer was constantly changing, the rats in the control group adapted more quickly. Their approach was more strategic.

" And when we analyzed their brain activity," explains this specialist in the biology of addiction, "the neural signals linked to decision-making were more intense in them ."

The team therefore linked these behavioral difficulties to marked functional alterations in a key brain region for decision-making: the dorsomedial striatum. Alcohol had disrupted neural circuits, reducing the efficiency of information processing in the exposed rats.

An explanation for the high risk of relapse

Months after withdrawal, the rats' brain activity during decision-making remained impaired. One surprising finding is that these cognitive deficits and neuronal alterations persisted well after alcohol cessation.

This phenomenon could explain why the risk of relapse is so high in people who have suffered from alcohol dependence. Thus, alcohol-induced neural deficits could influence the decision to drink, even after detoxification. " Our work clearly shows that these alterations can be long-lasting ," the researchers add.

One point to note: the behavioral and neural deficits were only observed in male rats. The researchers don't believe this means that females are protected from the effects of alcohol, but rather that there may be differences in sensitivity between the sexes.

The team now plans to explore how alcoholism affects other brain regions that interact with the dorsomedial striatum and to identify the mechanisms explaining these differences between males and females.