It all starts in a small region of the brain with an army of about 500 neurons. A new study published in Nature Neuroscience and conducted by the team of Gilles Martin, associate professor of Neurobiology at the University of Massachusetts (USA), has identified among the billions of neurons in the brain those responsible for the development of alcohol addiction.
While recent studies have highlighted specific areas of the brain, such as the prefrontal cortex, that play a role in inhibiting excessive alcohol consumption, these works had lacked the necessary precision to identify the specific neural circuits involved in suppressing alcohol consumption.
The new findings from the University of Massachusetts provide insights into excessive alcohol consumption behavior and alcohol dependence that can lead to new therapeutic targets. According to Martin, who is also a member of the Brudnick Neuropsychiatric Research Institute at the University of Massachusetts Chan, "It is really difficult to understand how only a few neurons, half a thousand, can have such a profound effect on behavior. We are beginning to understand how only a few cells participate in very specific behaviors."
The U.S. team managed to pinpoint the area of the brain responsible for suppressing excessive alcohol consumption to a specific neuronal ensemble through a combination of advanced fiber photometry, optogenetics, electrophysiology, and single-cell transcriptomic technologies with a viral vector approach.
How did they identify the 'responsible' neurons for alcoholism?
Neuronal ensembles, a discrete group of coactivated neurons, represent the basic units of neuronal code in the brain. These small neuronal groups function in coordinated and recurrent patterns, activating together to create a distinctive activity pattern, often in response to specific stimuli.
Using a special mouse model designed to label and manipulate neurons that are activated during a defined period of time, the researchers identified a small group of neurons activated in response to episodes of excessive alcohol consumption.
When the neurons are activated in these animal models, they emit an extremely bright fluorescent protein that can be observed using fiber photometry technologies. Since this occurs in real-time, scientists can accurately identify the neurons that are activated when the animal is exposed to a stimulus.
Subsequently, through optogenetic techniques that use light to safely activate cells in living animals, these neurons can be activated and deactivated, as if it were a switch. This allows scientists to observe potential behavioral changes and link them to specific brain neurons.
"This area of the brain seems to be closely related to the suppression of this behavior. It is possible that dysfunction of this mechanism is involved in alcohol dependence, and its reactivation could be a therapeutic target," explains Martin. Observing small subsets of neurons, thanks to technological development, allows this researcher to suggest that "there may be only two or three dozen neurons responsible for suppressing excessive alcohol consumption. Knowing which ones they are could be a fundamental step towards the development of specific therapies."
Alcohol Consumption: A Public Health Problem
Alcohol addiction and its excessive consumption constitute a serious health problem, causing millions of deaths, both directly and indirectly, through more than 200 diseases and associated injuries derived from short and long-term consumption. According to data from the World Health Organization (WHO), alcoholism causes more than 3 million deaths annually worldwide. It also estimates that 400 million people live with alcohol-related disorders, and of these, 209 million suffer from dependence.
A concerning fact is that this consumption is increasingly being recorded in minors. According to data from the document Monograph on alcohol 2024: Consumption and consequences, issued by the Ministry of Health last year, 30% of minors aged 12 and 13 admit to having consumed alcohol at least once in the past year.
Studies conducted by the Addiction and Degenerative Disorders Neuropharmacology Group (Neurofan) at the Faculty of Pharmacy of the CEU San Pablo University in Madrid, led by Professor Gonzalo Herradón, provide more evidence: 28.2% of students between 14 and 18 years old admit to having engaged in 'binge drinking': consuming five or more drinks in a span of approximately two hours.
As indicated to this medium, "a binge episode - in this case 'botellón' - is defined as 5 alcohol units in men and 4 in women within a 2-hour interval, with the unit being around 100 ml of wine or 250-300 ml of beer." This type of consumption - excessive and intermittent - is the most damaging to the adolescent brain, according to the professor at CEU San Pablo.