A team of scientists from the Oregon National Primate Research Center at Oregon Health and Sciences University has found that a gene called the G-protein coupled receptor 39 (GPR39) had lower expression in the brains of nonhuman primates that voluntarily consumed heavy amounts of alcohol compared with those that drank less. Furthermore, the researchers unraveled a link between alcohol and how it modulates the levels of GPR39 activity. They discovered that when they increased the levels of the gene encoded protein in mice, they reduced alcohol consumption by almost 50% without affecting the total amount of fluid consumed or their overall well-being.
Cuzon Carlson et al identify a gene that could provide a new target for developing medication to prevent and treat alcohol use disorder, a chronic condition with devastating health and socioeconomic effects. Image credit: Imagens Evangelicas / CC BY 2.0.
“Our study highlights the importance of using cross-species approaches to identify and test relevant drugs for the treatment of alcohol use disorder,” said Dr. Rita Cervera-Juanes, senior author of the study.
Dr. Cervera-Juanes and colleagues modified the levels of the protein encoded by GPR39, which is a zinc-binding receptor previously associated with depression.
The prevalence rates of co-occurring mood and alcohol use disorders are high, with individuals with alcohol use disorder being 3.7 times more likely to have major depression than those who do not abuse alcohol.
Using a commercially available substance that mimics the activity of the GPR39 protein, the team found that targeting this gene dramatically reduced alcohol consumption in mice.
To determine whether the same mechanism affects people, the scientists are now examining tissue samples from the brains of people who suffered from alcoholism.
Currently, there are only a handful of treatments for alcoholism approved by the Food and Drug Administration (FDA).
By testing the effect of the substance in reducing ethanol consumption in mice — in addition to its previously reported link in reducing depression-like symptoms — the findings may point the way toward developing a drug that both prevents and treats chronic alcoholism and mood disorders in people.
“We are finding novel targets for which there are drugs already available, and they can be repurposed to treat other ailments,” Dr. Cervera-Juanes said.
“For alcoholism, this is huge because there are currently only a handful of FDA-approved drugs.”
The study was published in the journal Neuropsychopharmacology.
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Verginia C. Cuzon Carlson et al. Modulation of Gpr39, a G-protein coupled receptor associated with alcohol use in non-human primates, curbs ethanol intake in mice. Neuropsychopharmacology, published online January 5, 2019; doi: 10.1038/s41386-018-0308-1
