Scripps Research Scientists claim they have managed to curb alcohol-seeking behaviors in rats with alcohol addiction by activating a receptor found in brain cells. This receptor may someday be used as a target to treat alcohol addiction and ease withdrawal symptoms. The findings can be found in a paper published in eNeuro.
Alcohol use disorder affects an estimated 15 million adults in the United States; today there are three medications approved by the FDA to treat alcohol addiction, but each has its limitations.
This research stems from a 2005 study in which researchers sifted through the human genome for new receptors resembling known receptors. They found a GPC-like receptor, which they called GPR139, and was eventually shown to be primarily located in an area of the brain called the habenula. The habenula is known to be activated during drug and alcohol withdrawal, leading the scientists to suspect GPR139 may be involved in addiction.
To test this, they orally administered an experimental compound that activates GPR139, called JNJ-63533054, to 12 non-alcohol-dependent male rats and 17 alcohol-dependent rats. The did not affect alcohol or liquid consumption in non-alcohol-dependent rats, but it significantly decreased the alcohol intake of the dependent rats. This was particularly true in those with the highest alcohol intake who showed the most compulsive drinking behavior—these would continue drink even when a bitter taste was added to the alcohol.
Pain threshold is known to decrease when going through alcohol withdrawal, so the next step was for the researchers to track pain threshold in the 17 rats going through withdrawal. Rats treated with JNJ-63533054, particularly those with the highest addiction levels, had a higher threshold for pain, showing again that the compound can alleviate symptoms of withdrawal. Further studies in which the compound was administered to different areas of the brain revealed that treatment only worked when applied to the habenula, confirming the importance of this region in addiction and withdrawal.
The researchers believe these findings will extend beyond males to both males and females and suspect the pathway is involved in other addiction disorders beyond alcohol dependence. They plan is to continue this research in the future.