Better knowledge of how the mechanism explaining alcohol addiction works

Alcohol, like any other substance that reinforces behaviour, such as another drug of abuse or even food, has a certain capacity to enhance social memory, that is, the ability to remember other individuals. If a mouse is administered alcohol immediately after being introduced to another animal of its own kind, the former will recognise the latter sooner.

This phenomenon, which has significant implications when it comes to understanding the process underlying alcohol addiction, does not have a definitive explanation. However, a team of researchers from the Psychobiology Department at the University Jaume I (Spain) has revealed a part of the mystery, since they have proved that the substance responsible for enhancing social memory is not ethanol, but another compound derived from alcohol metabolism in the brain, namely, acetaldehyde.

The UJI team, headed by Psychobiology Professor Carlos González Aragón, has been working for years conducting experiments to prove that alcohol is metabolised not only in the liver but also in certain areas of the brain where important amounts of ethanol are processed through the action of an enzyme known as catalase. The substance derived from these reactions, acetaldehyde, is involved in many of the changes of behaviour typically associated to alcohol. Catalase metabolises alcohol in the brain and gives rise to a certain amount of acetaldehyde that, according to the researchers, would be responsible for the effects attributed to ethanol. If substances that enhance the action of catalase are administered, a higher production of acetaldehyde and a boost in its effects are observed, while acetaldehyde and most of the effects of ethanol are not produced when catalase inhibitors are used after having consumed a certain amount of alcohol.

Up to now, however, researchers had proved that brain catalase was involved in the stimulating effect of ethanol, but its role in complex cognitive processes such as learning and memory had not been dealt with. The work that we are now bringing to light, and which is the main point in the thesis of researcher Héctor Marín, proves this involvement. By administering catalase enhancers and inhibitors to mice, Marín has shown how the enzyme intervenes in the reinforcement of social memory.

“This is the first study that demonstrates that the manipulation of brain catalase activity and, therefore, the presumable production of acetaldehyde in the brain, modifies the effects of ethanol on memory. In other words, the facilitating effect that ethanol has on social memory needs to previously metabolise it into acetaldehyde with the mediation of the catalase enzyme in the brain”, explains Héctor Marín.

In a first stage of the experiment, the researchers proved the enhancing effect exerted by alcohol on social memory by administering a certain dose of ethanol to an adult mouse after a first contact with a younger one. “We saw how ethanol injected into the mouse immediately after being introduced to the young mouse was able to double the capacity of the adult mouse to recognise the younger one, that is, to remember this previously introduced rodent-stimulus”, Marín points out.

In a second stage, the researchers at the UJI repeated the experiment, but they administered some catalase inhibitors to the adult mouse, and enzyme activity was thus severely limited. The results showed that, even though the rodent’s brain was receiving the same amount of alcohol as in the previous experiment, the ability of the adult mouse to remember the younger one was the same as that of a mouse that had not been injected with alcohol. “This suggests that our pre-treatments with catalase inhibitors do not modify the concentration of alcohol that reaches the brain from the bloodstream; rather, what they do is modify the ability of catalase to transform this ethanol into acetaldehyde directly in the brain,” adds Héctor Marín.

For the researchers, the results of the study have significant implications in the knowledge of how the mechanism explaining alcohol addiction works. In actual fact, every reinforcing substance has some memory enhancing effects and the way in which a particular drug affects the memory processes may be fundamental in order to understand its addictive power, claim the UJI researchers. In this case, some authors are beginning to replace the concept of alcoholism with that of acetaldehydism, for the very reason that acetaldehyde could play a key role in the development of addiction to alcohol. “If this is true, blocking the production of acetaldehyde directly in the brain could protect against or prevent alcoholism”, concludes Marín.