Currently, there are only three FDA-approved medications for reducing alcohol cravings — all targeting addiction as a brain-based disorder. A new interdisciplinary study from Brigham Young University, however, opens an angle of neuroimmune research that could potentially lead to better medical treatments.

This collaborative research involved 13 students and four professors across three departments in the College of Life Sciences and the College of Family, Home, and Social Sciences.

While neuroimmune research is on the rise, this is the first study to explore whether alcohol consumption might involve neuroimmune mechanisms. In particular, the researchers explored how immune cells function relative to dopamine levels.

“The scientific community knows a bit about the reward circuitry of the brain,” said coauthor Jeff Edwards, a BYU professor of cell biology and physiology. “There are two different circuits in the brain’s reward center — one directly causes an increase in dopamine, and the other inhibits dopamine through GABA, the brain’s calming neurotransmitter; if you decrease the GABA neurotransmitter system, dopamine can go up.”

Because alcohol does not elevate dopamine from increased dopamine cell activity directly, the team focused on how alcohol affects the GABA-mediated circuit and how altering the immune system might reveal some mechanistic clues. To test this, they examined a population of male and female mice in which CD5, a protein found on white blood cells, was genetically disabled. All mice were bred, housed and handled in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Researchers then assessed how the CD5 “genetic knockout” influenced alcohol reward, sedation, and consumption.

The methods and results were as follows:

• Mice were provided food, water and alcohol over three weeks. The CD5-knockout mice drank the same amount of water but significantly less alcohol.
• Electrical recordings were taken from the mice brains. The genetic knockout led to functional changes in dopamine and GABA cells.
• Researchers measured decreased activity and loss of ability to return to normal posture in the knockout mice.
• Blood alcohol levels were measured, and the knockout mice showed no difference in the rate of alcohol metabolism.

“We found there was less of an alcohol reward in the mice population that had CD5 removed from their immune cells; so eventually they didn’t drink as much,” said coauthor a Scott Weber, a BYU professor of microbiology and molecular biology. “We don’t currently have it all solved, but if we are able to identify the mechanism of how this works, an immunotherapy could be developed down the road that may make it easier for people to break this addictive alcohol cycle.”

Now a professor at Noorda College of Osteopathic Medicine, first author Andrew Payne reflects on his time at BYU as a period of intellectual and spiritual growth strengthened by lasting connections to mentors and peers. He expects their work will help pave the way for treatments that alleviate suffering.

“Addiction represents a set of disorders that are remarkably difficult to overcome, and new treatment options are sorely needed,” Payne said. “We need as much understanding as we can get of how the brain and body respond to substances of abuse so that we can inform the next generation of treatment options.”

BYU Professor Emeritus Scott Steffensen (Psychology) and former BYU professor Jordan Yorgason (Wake Forest University School of Medicine) were also co-authors on the research article.