Researchers identify the anti-inflammatory mechanisms that drive alcohol addiction

Reviewed by Emily Henderson, B.Sc.November 17, 2020

Deep inside the brain, a small almond-shaped region called the amygdala plays a vital role in how we exhibit emotions, behavior and motivation. Understandably, it is also heavily implicated in alcohol abuse, making it a long-time target of Marisa Roberto, Ph.D., professor in the Department of Molecular Medicine at Scripps Research.

Now, for the first time, Roberto and his team have identified important changes in the anti-inflammatory mechanisms and cellular activity of the amygdala that drive alcohol addiction. By counteracting this process in the mice, they were able to stop excessive alcohol consumption, revealing a potential treatment path for alcohol use disorder. The study is published in Advances in Neurobiology.

We found that chronic exposure to alcohol compromises the brain’s immune cells, which are important for keeping neurons healthy. The resulting damage fuels anxiety and alcohol consumption which can lead to an alcohol use disorder. “

Reesha Patel, PhD, Study First Author and Postdoctoral Fellow, Roberto’s Laboratory

Roberto’s study specifically looked at an immune protein called interleukin 10, or IL-10, which is prevalent in the brain. IL-10 is known to have powerful anti-inflammatory properties, which ensure that the immune system does not respond too strongly to disease threats. In the brain, IL-10 helps limit inflammation from injury or disease, such as stroke or Alzheimer’s. But it also appears to influence key behaviors associated with chronic alcohol use.

In mice with chronic alcohol consumption, IL-10 was significantly reduced in the amygdala and did not signal correctly to neurons, contributing to the increase in alcohol intake. By increasing IL-10 signaling in the brain, however, scientists could reverse the aberrant effects. In particular, they observed a sharp reduction in anxious behaviors and motivation to drink alcohol.

“We have shown that inflammatory immune responses in the brain are very much at play in the development and maintenance of alcohol use disorder,” says Roberto. “But perhaps more importantly, we have provided a new framework for therapeutic intervention by pointing to anti-inflammatory mechanisms.”

Alcohol use disorder is widespread, affecting approximately 15 million people in the United States, and few effective treatments exist. By examining how brain cells change with prolonged exposure to alcohol, Roberto’s lab has discovered many possible new therapeutic approaches for people with alcohol addiction.

In the latest study, Roberto’s lab collaborated with Silke Paust, Ph.D., associate professor in the Department of Immunology and Microbiology. Paust and his team determined the precise immune cells throughout the brain that are affected by chronic alcohol use.

The results revealed a major shift in the brain’s immune landscape, with increased levels of immune cells known as microglia and regulatory T cells, which produce IL-10.

Despite a greater number of IL-10-producing cells in the entire brains of mice with prolonged alcohol use, the amygdala told a different story. In that region, IL-10 levels were lower and their signaling function was impaired, suggesting that the immune system in the amygdala uniquely responds to chronic alcohol consumption.

This study complements the recent findings from the Roberto laboratory that demonstrate a causal role of microglia in the development of alcohol addiction.

Future studies will build on these findings to identify exactly how and when IL-10 signals neurons in the amygdala and other addition-related brain circuits to alter behavior.