AUD is characterized by binge drinking and compulsive drinking, and encompasses a variety of conditions including alcohol abuse, dependence, and binge drinking. Researchers have previously discovered numerous links between the immune system and AUD, many of them centering on IL-1β. People with certain mutations in the gene that codes for the IL-1β molecule, for example, are more likely to develop AUD. Also, autopsies of people who had AUD have found higher levels of IL-1β in the brain.
Scripps Research scientists have discovered new details about the role of the immune system in this cycle. The immune signaling molecule interleukin 1β (IL-1β) is present at higher levels in the brains of alcohol-dependent mice. Furthermore, the IL-1β pathway takes on a different role in these animals, causing inflammation in critical areas of the brain known to be involved in decision making.
In this new study, they compared alcohol-dependent mice with animals that drank moderately or not at all. They found that the alcohol-dependent group had about twice as much IL-1β in the medial prefrontal cortex (mPFC), a part of the brain that plays a role in regulating emotions and behaviors.
The team then showed that IL-1β signaling in the alcohol-dependent group was not only increased, but also fundamentally different. In mice that had not been exposed to alcohol, as well as in mice that had drank moderate amounts of alcohol, IL-1β activated an anti-inflammatory signaling pathway. In turn, this reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), a signaling molecule known to regulate neural activity in the brain.
However, in alcohol-dependent mice, IL-1β activated proinflammatory signaling and increased GABA levels, likely contributing to some of the changes in brain activity associated with AUD. Notably, these changes in IL-1β signaling in the alcohol-dependent mice persisted even during alcohol withdrawal.
Drugs that block IL-1β activity are already approved by the US Food and Drug Administration to treat rheumatoid arthritis and other inflammatory conditions. More work is needed to determine if these existing drugs might be useful in the treatment of AUD.
These findings were reported in the journal Brain, Behavior and Immunity.