behavioral causes and consequences that depend on gender? ⋅ Inserm, Science for health

After several weeks of binge drinking, male rats exhibit impaired decision-making ability. A phenomenon that is not found in females. The processes in question could be transposed to humans and, thus, explain the greater vulnerability of men in the face of this behavior dangerous to health.

The massive and rapid consumption of alcohol, also called binge drinking, exposes you to medical risks. Defined by the regular absorption (twice a month or more) of at least 6 glasses in 2 hours, this behavior would notably multiply by three the risk of 18–25 year olds of developing alcohol dependence. alcohol and drug addictions, led by Mickaël Naassila, works to understand this practice and its consequences. In a recent study, the researcher and his team wanted to decipher the role of decision-making in this evolution: “ Decision-making is the cognitive process that allows us to make the most beneficial choices for our daily lives when we have several alternatives.explains the researcher. It can be assessed by a simple test, the Iowa Gambling Task: Individuals are placed in front of 4 piles of cards, face down. In two of these piles, the cards are associated with the probability of winning a lot of money, but also with the probability of losing a lot. Persevering in drawing cards from these piles leads to losing at the end of the game. The cards from the other two piles reward less, but they are “safer”. The person taking the test does not know these probabilities at the beginning of the experiment: he must therefore adapt his behavior as he makes his choices. However, several studies have shown that those who regularly practice binge drinking perform worse on this test because they persist in choosing “at risk” batteries. Other work suggests an association between having poor decision-making skills and vulnerability to heavy drinking. It is therefore possible that a vicious circle exists between the two behaviors: the binge drinking would alter decision-making, which would itself favor excessive consumption. But there is still a lack of data to confirm this hypothesis, both in humans and in animals.

A pre-existing gender difference

To find out more, Mickaël Naassila and his team worked on the preclinical rat model. They first gave the animals access to a 20% alcoholic drink, placed in their housing cage every other day for a month. For the next two months, access to alcohol was limited to only 15 minutes a day – in the manner of the famous “happy hours” – to trigger a type of behavior binge drinking. The researchers then observed a relatively homogeneous behavior in all the rodents, which indulged in this way of consuming in an equivalent way. All animals were then subjected to a decision-making test comparable to the Iowa Gambling Task: “The rats had four options to choose from that get sugar with different probabilities. But those that offer the greatest number of rewards are associated with penalties, in this case a delay before obtaining a new reward. » So much so that at the end of the test, these options turn out to be less favorable.

The researcher and his team have observed that the results of this experiment are influenced by the sex of the animals, including when it is conducted before any access to alcohol: “ Female rats more often prefer safer options than malesexplains Mickaël Naassila. This difference also exists in humans, suggesting that this trait may have biological components that have yet to be established. It could be explained by the role of dopamineand neurotransmitter involved in decision-making processes and in the attraction of rewards, which is regulated by female hormones (estrogen).

An alteration related to binge drinkingonly in males

Regardless of their gender, “no correlation between decision-making abilities before the onset of alcohol consumption and the behavior of binge drinking later was observed. This indicates that poor decision-making abilities are not the cause of vulnerability to binge drinking”, also reports the researcher. On the other hand, the binge drinking seems to induce an alteration of these capacities, only in males, and unrelated to the existence of anxiety or cognitive disorders.

The researchers finally took the animals’ brains, in order to study the activity of the neurons of the nucleus accumbens, a brain region in which dopamine is released and which plays a major role in the pleasant effects of alcohol and the repetition of its consumption. They analyzed the activity of these neurons after the binge drinking and compared it to that observed in animals that had never consumed alcohol: no modification of the release of dopamine was observed, either in males or in females. However, in the latter, the binge drinking chronic changes the response of dopamine receptors carried by neurons. It remains to explain its origin and consequences.

Understanding Male Vulnerability

« We think it possible that females are less sensitive to the effects of binge drinking because they initially have better decision-making abilities than males sums up the researcher. Today, he wishes to complete this work, in particular by studying the neuronal activity linked to dopamine directly in the brain of living animals: “ Such experiments would make it possible to analyze the processes dopaminergic in a more integrated model, which includes all of the neural networks. The researchers also want to explore more precisely the vulnerability of certain groups of animals to excessive alcohol consumption, depending on their decision-making abilities, as well as the possible protective role of good cognitive abilities.

These findings also motivate the team to explore sex-linked divergences in humans. ” Of the prospective studies would make it possible to follow young people before any alcohol consumption, then after a behavior of several months of binge drinkingto look for a possible causality between this practice and the evolution of their decision-makinghe reports. It would also be interesting to extend this follow-up to the evaluation of their behavior and their academic results. »

The greater vulnerability of the male sex to the consequences of binge drinking suggests looking more readily at this population and considering targeted preventive approaches. Understanding the elements underlying this relationship could help public authorities to propose awareness-raising or prevention actions aimed at vulnerable populations. Because the stakes are high, as suggested by the researcher’s previous work: ” The comparison of binge drinkers twenty years to young people who drink more slowly shows the impact of the rate of alcoholization: we observe in the former an alteration of the substance blanche of the cerebral cortex, which controls the executive functionsand a decrease in memory performance “, insists Mickaël Naassila. The end of adolescence being a particular phase of neurodevelopment, it could constitute a critical period during which the toxicity of acute alcoholism has a particularly harmful impact on brain tissue.

Mickael Naassila is Director of the Research Group on Alcohol and Drug Dependence