Alcohol use disorder: A step toward better treatment?
A doctor diagnoses alcohol use disorder (AUD) when an individual’s use of alcohol becomes compulsive.
Someone with AUD feels intense cravings for alcohol and, when none has been consumed, experiences symptoms of withdrawal.
According to the National Institute on Alcohol Abuse and Alcoholism, there are around 16 million people in the United States with AUD.
Mood disorders, including depression and bipolar disorder, are often linked with AUD but are even more prevalent. The National Institute of Mental Health estimate that mood disorders affected 9.7 percent of adults in the U.S. between 2016 and 2017.
AUD and mood disorders
The links between AUD and mood disorders were described decades ago. However, it has been difficult to tease apart cause and effect: Drinking excessive amounts of alcohol can produce depression-like symptoms and, because alcohol alters mood, some people with mood disorders self-medicate with alcohol.
Recently, researchers from the Oregon Health & Science University in Portland set out to investigate novel ways of approaching AUD. Specifically, they studied a zinc-binding receptor called G-protein coupled receptor 39 (GPR39), which scientists had previously linked to depression.
The researchers behind the new study published their results in the journal Neuropsychopharmacology.
Some individuals are more likely to drink alcohol excessively than others; these interpersonal differences are not unique to humans. For instance, in a previous study, the authors investigated the effects in rhesus macaques.
The researchers showed that rhesus macaques with a natural propensity to drink more alcohol had reduced GPR39 activity. They theorized that a compound that enhanced GPR39 activity might reduce alcohol intake.
Reactivating GPR39
To test their hunch, the researchers used a commercially available chemical called TC-G 1008 that binds to and activates GPR39. When they gave the substance to mice, they found that it significantly reduced the amount of alcohol that the mice consumed.
In fact, alcohol consumption dropped by 47 percent. The researchers also noted that the drug did not otherwise alter the animals’ behavior or reduce overall fluid intake.
Importantly, repeat doses kept alcohol consumption to a lower level. The authors also demonstrated that once TC-G 1008 was flushed from the system, alcohol consumption resumed at its pretreatment levels.
In addition, the researchers noted that increased activity of GPR39 correlated with increased glutamate activity in a part of the brain called the nucleus accumbens.
Glutamate is the primary excitatory neurotransmitter in the brain, and the nucleus accumbens, which is involved in reward and reinforcement, has previously been implicated in alcohol misuse.
The authors believe that TC-G 1008’s effect on alcohol consumption may be due to changes in the levels of excitation and inhibition in the nucleus accumbens.
“The study highlights the importance of using cross-species approaches to identify and test relevant drugs for the treatment of alcohol use disorder.”
Senior author Rita Cervera-Juanes, Ph.D.
From laboratory to human
The next phase, of course, is to examine this mechanism in humans. Already, the researchers are studying brain tissue from individuals with AUD.
The reasons why addictions appear in some individuals and not others are varied and interweaved; early experiences, psychological traits, traumatic life events, and genetic susceptibilities are all knitted together.
Finding a drug that can untangle these strands and remove AUD is incredibly unlikely; however, finding a compound that might, at the very least, remove some of the urges associated with AUD would be welcome indeed.
The authors hope that by modulating GPR39, they might find new ways of treating AUD and mood disorders. Because both types of condition are difficult to treat effectively, finding new potential avenues of investigation is exciting.
As Cervera-Juanes concludes, “We are finding novel targets for which there are drugs already available, and they can be repurposed to treat other ailments. For alcoholism, this is huge because there are currently only a handful of [U.S. Food and Drug Administration (FDA)]-approved drugs.”
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