People with alcohol addiction, which is known as alcohol use disorder or alcoholism, are immersed in a kind of vicious circle based on the changes that this substance produces in their brain and in their behavior, since this disorder can modify signaling pathways in the brain and these alterations can potentiate alcohol consumption.
A new study has now revealed the role the immune system plays in this process; Specifically, he has discovered that in the brains of alcohol-dependent mice, the levels of interleukin 1β (IL-1β) –an immune signaling molecule– are higher, and that its function is also different in these animals and causes inflammation in key areas of the brain involved in decision making. Their results have been published in Brain, Behavior and Immunity and point to a potential new drug target for the treatment of alcoholism.
“These inflammatory changes in the brain could explain some of the risky decision-making and impulsiveness we see in people with alcohol use disorder,” says lead author Marisa Roberto, Chair of Schimmel Family Molecular Medicine and Professor of neuroscience at Scripps Research. “In addition, our findings are incredibly exciting because they suggest a potential way to treat alcohol use disorder with existing anti-inflammatory drugs that target the IL-1β pathway.”
A new approach to address alcohol use disorder
Alcohol use disorder (AUD) is characterized by impulsive and uncontrolled drinking, and includes problems such as alcohol abuse, dependence, and excessive alcohol consumption. Scientists have previously discovered numerous links between the immune system and this disorder, many of them centered on IL-1β; Thus, for example, individuals with certain mutations in the gene that encodes the IL-1β molecule are more likely to develop it. In addition, autopsies of people with AUD have found higher levels of IL-1β in the brain.
The alcohol-dependent group had about twice the amount of IL-1β in an area of the brain involved in regulating emotions and behaviors
“We suspected that IL-1β was playing a role in AUD, but the exact mechanisms in the brain were unclear,” says first author Florence Varodayan, an assistant professor at Binghamton University and a former postdoctoral fellow in Roberto’s lab.
The authors of the new study compared alcohol-dependent mice with conspecifics that drank moderately or never drank alcohol and found that the alcohol-dependent group had about twice the amount of IL-1β in the medial prefrontal cortex (mPFC), an area of the brain involved in regulating emotions and behaviors.
They subsequently demonstrated that IL-1β signaling in the alcohol-dependent group was not only increased but also significantly different, since IL-1β activated an anti-inflammatory signaling pathway both in mice that had not been exposed to alcohol, as in those who had drunk moderate amounts of alcohol. This, in turn, decreased levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), a signaling molecule that regulates neuronal activity in the brain.
In contrast, in the alcohol-dependent mice, IL-1β activated proinflammatory signaling and increased GABA levels, likely facilitating some of the AUD-related changes in brain activity. These changes in IL-1β signaling in the alcohol-dependent mice were maintained even during alcohol withdrawal.
The good news is that drugs that block IL-1β activity are already approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis and other inflammatory conditions, although more research is needed to determine whether these drugs could be useful in the treatment of alcohol use disorder.
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