Treatment of alcoholism: a new target

Alcoholic mice helped to look into the root of addiction

Daria Zagorskaya, Vesti

The history of winemaking and brewing dates back to the Neolithic era, numbering more than one thousand years. And soon after people discovered that fermented grape juice has a very interesting effect, the first alcoholics appeared.

Today, scientists know that the pathological attraction to alcohol occurs not only in humans, but also in many animals. For example, laboratory mice that get access to alcohol very quickly begin to show signs of addiction.

It is also known that the action of most narcotic substances, directly or indirectly, is directed at the brain's reward system. They contribute to the intense release of neurotransmitters that cause a feeling of pleasure. But a fairly simple ethanol molecule does not have a specific place of action, and until now it remained unclear how it changes the work of the brain and leads to uncontrolled alcohol consumption.

"Now the media is paying a lot of attention to drug addiction," he says Dorit Ron from the University of California in San Francisco, the author of a new work. – But alcohol abuse is a much more serious problem, from which 3.3 million people die every year. Unfortunately, there are only a few drugs on the market to reduce the level of addiction, but they all do not work well enough."

Previous work with rodents has led researchers to the idea that a protein codenamed mTORC1 can act as an intermediary between many drugs and brain centers. In particular, Ron and her colleagues found that excessive alcohol consumption increases the activity of this protein in the nucleus accumbens, a group of brain neurons involved in the reward system and the formation of a sense of pleasure. As a result, a number of structural changes occur in the brain that cause positive associations with alcohol.

In further experiments, the researchers also learned to block cravings for alcohol by suppressing the activity of mTORC1 with the drug rapamycin. But this immunosuppressant shows several severe side effects and is not suitable for the treatment of alcoholism in humans. Therefore, Ron and her colleagues, in order to find safer medicines, decided to understand in more detail the role of protein in the formation of alcohol dependence.

In the absence of bad habits, mTORC1 participates in the synthesis of new proteins, so scientists decided to look for molecules in the brains of "drinking" mice, the production of which increases with alcohol consumption. Using the RNA sequencing method, they isolated 12 such substances, among which the ProSAPiP1 protein attracted special attention. Its exact role remained unclear, but it was known from previous works that it was somehow connected with the synapses of neurons (places where they connect to each other).

When the scientists again allowed the mice to plunge into the abyss of binge drinking, it turned out that it was ProSAPiP1 that changed the structure and functions of the neurons of the nucleus accumbens. After that, the rodents, who were offered a choice between water and alcohol, were increasingly inclined in favor of the latter.

In the second stage of the experiment, Ron's team bred a line of genetically modified mice that could not synthesize ProSAPiP1. It turned out that these animals were not inclined to go all out and preferred water much more often than their ordinary counterparts.

It is worth noting that protein blocking did not affect the rodents' addiction to sweets in any way. They willingly consumed a sugar solution, which also causes a positive reaction in the pleasure centers.

"We have identified a new protein that plays a crucial role in changing the landscape of the neurons of the nucleus accumbens, which then leads to a craze for problem drinks," explains Ron. "These results reveal how alcohol and other drugs harm our brain."

Now scientists hope that the discovery of a molecular pathway for the formation of alcohol dependence will soon allow us to develop a new approach to its treatment.

The detailed results of the study were published in the journal Neuron.

Portal "Eternal youth" http://vechnayamolodost.ru  12.09.2017