Research carried out in the Laboratory of Molecular Basis of Behavior, describes cellular processes specific to the brain of alcohol addicted mice.

The behavior of an alcohol addict is extremely stereotypical. Most of their activities and thoughts are focused on drinking. Encountering people, things, and sometimes seemingly insignificant events, reminds them of alcohol, increasing the craving to drink. For an alcoholic, everything that is not associated with drinking becomes less important. Family, work, and health become insignificant.

Today we know that alcoholism is a serious mental illness, not a weak character. However, we still don’t know why some people can drink alcohol throughout their lives. Some control when and how they drank, and they derive pleasure from it, while for others drinking becomes a tragic game, during which one can lose not only friends, but also your own life. Unfortunately, most of the available medications work only to a very limited extent, and psychotherapy is the only hope for help. Why are the medications not effective? First of all, because addiction is a disease with a very complex biological background, and we still do not know its cellular and molecular bases.

Can animal research bring us closer to understanding how the brain of an alcoholic works?

Dr Kasia Radwańska, together with prof. Leszek Kaczmarek, developed a series of tests analyzing alcohol addiction-related behaviors in rodents (Radwańska and Kaczmarek, Addiction Biology 2012). Using automatic IntelliCage system, it is possible to examine not only how much alcohol an individual mouse drinks, but also whether they are highly motivated to seek alcohol during periods of withdrawal, or whether the behavior of a drinking mouse becomes stereotypical (not flexible and focused on seeking and drinking alcohol), how does the mouse react to stimuli associated with alcohol, and whether such stimuli can trigger relapse. Thanks to such precise analysis of behavior, it is possible to select from the mouse population those individuals that resemble alcoholics, and examine what changes occur in their brains.

A team of researchers led by Kasia Radwańska used this model to investigate functional changes in the hippocampus of mice identified as addicted to alcohol.

„The hippocampus is a brain area traditionally associated with memory formation and the creation of a ‚space map’. Our research has shown, however, that in hippocampus there are processes specific to addicted individuals. For example, when we exposed an addicted mouse to an alcohol-associated stimulus – a light that signaled the availability of alcohol – we found that silent synapses were formed in the hippocampus, „said Dr. Radwańska, head of the Laboratory of Molecular Basis of Behavior.

Why are silent synapses important?

„Neurons communicate via synapses. Most synapses in the brain of an adult individual are mature and are able to transfer information between nerve cells through receptor activation. In this process, the most important are AMPA and NMDA receptors for glutamate. We have shown that in the brain of an alcoholic mouse „silent synapses” are formed. In those contacts there are no functional AMPA receptors, hence they do not participate in basal synaptic transmission. Interestingly, more such synapses are induced in the brain of alcohol-addicted mice than in the brains of mice that drink sweet water or consume alcohol moderately. The formation of silent synapses indicates that the nervous system undergoes functional changes. My previous research has shown that silent synapses can mature into functional connections. More and more reports demonstrate, that the maturation of silent synapses can contribute to the development of drug craving. We were the first to show that in hippocampus silent synapses induced during alcohol relapse are specific for addicts, „explained Dr. Anna Beroun from the Laboratory of Neurobiology.

Is it possible to block the formation of silent synapses in individuals who drink alcohol?

„In our research, we used acamprosate, a drug that reduces alcohol consumption, and prolongs the abstinence of addicts. Interestingly, although it is a drug approved for use in therapy, we still lack the understanding of the mechanism of its action. We administered acamprosate to mice identified as addicted. Acamprosate reduced alcohol consumption in addicted mice, and analysis of hippocampal cell function showed that silent synapses were not present. Understanding the molecular processes regulated by acamprosate may deepen our knowledge of the molecular basis of addiction.” commented Maria Nalberczak-Skóra from the Laboratory of Molecular basis of Behavior.

In this year’s edition of the competition for the Jerzy Konorski prize, awarded by the Polish Neuroscience Society and the Committee of Neurobiology of the Polish Academy of Sciences, a study describing the formation of silent synapses in the hippocampus of addicted mice has been distinguished „Generation of silent synapses in dentate gyrus correlates with the development of alcohol addiction.” By Anna Beroun, Maria Nalberczak-Skóra, Zofia Harda, Małgorzata Piechota, Magdalena Ziółkowska, Anna Cały, Roberto Pagano and Kasia Radwańska in the Neuropsychopharmacology journal (volume 43, 1989–1999, doi:10.1038/s41386-018-0119-4).

Contact:

Dr hab. Katarzyna Radwańska
Laboratory of Molecular Basis of Behavior
k.radwanska@nencki.edu.pl

Read more: https://www.focus.pl/artykul/pigulka-na-alkoholizm?page=4

About the Laboratory of Molecular Basis of Behavior: https://radwanskalab.eu/

About the Jerzy Konorski Award: http://www.ptbun.org.pl/?lang=pl&a=konor