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For people with alcohol use disorder (AUD), there is a
constant, vicious cycle between changes to the brain and
changes to behavior. AUD can alter signaling pathways in the
brain; in turn, those changes can exacerbate drinking.
Researchers have uncovered new details about the immune
system's role in this cycle that the immune signaling
molecule interleukin 1ß (IL-1ß) is present at higher levels
in the brains of mice with alcohol dependence. In addition,
the IL-1ß pathway takes on a different role in these
animals, causing inflammation in critical areas of the brain
known to be involved in decision-making. These inflammatory
changes to the brain could explain some of the risky
decision-making and impulsivity we see in people with
alcohol use disorder. AUD is characterized by uncontrolled
and compulsive drinking, and it encompasses a range of
conditions including alcohol abuse, dependence and binge
drinking. Researchers have previously discovered numerous
links between the immune system and AUD many of them
centered around IL-1ß. People with certain mutations in the
gene that codes for the IL-1ß molecule, for instance, are
more prone to developing AUD. In addition, autopsies of
people who had AUD have found higher levels of IL-1ß in the
brain. The team then went on to show that IL-1ß 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 drunk moderate
amounts of alcohol, IL-1ß activated an anti-inflammatory
signaling pathway. In turn, this lowered 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-1ß instead
activated pro-inflammatory signaling and boosted levels of
GABA, likely contributing to some of the changes in brain
activity associated with AUD. Notably, these changes in
IL-1ß signaling in the alcohol-dependent mice persisted even
during alcohol withdrawal. |