Having a few drinks with friends is a regular part of social life for many individuals, but for over 7% of adults in the US, just a “few drinks” can quickly turn into problem drinking or alcohol use disorder. Now, researchers publishing in the journal Molecular Psychiatry have found that a small segment of genetic material known as microRNA is integral in the transition from moderate drinking to problem drinking.
According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), in 2012, 17 million adults in the US aged 18 and over had an alcohol use disorder (AUD).
Adults, however, are not the only group affected; the NIAAA report that in 2012, an estimated 855,000 adolescents between the ages of 12 and 17 also had an AUD.
To further investigate potential mechanisms in the brain that play a role in such disorders, Dorit Ron, Endowed Chair of Cell Biology of Addiction in Neurology from the University of California-San Francisco (UCSF), and colleagues looked at a protein known as brain-derived neurotrophic factor (BDNF).
In previous studies, she and her team have demonstrated that the level of BDNF increases in the brain when alcohol is consumed in moderation, and that the protein prevents the development of AUDs.
For their latest study, the researchers observed that there was a significant decrease in the amount of BDNF in the medial prefrontal cortex (mPFC) – a brain region involved in decision making – when mice consumed excessive amounts of alcohol for prolonged periods.
In turn, this decrease was linked to a corresponding increase in the level of a microRNA known as miR-30a-5p, the team reports.
Ron and her colleagues explain that microRNAs lower the levels of proteins – such as BDNF – by binding to messenger RNA. These messenger RNAs act as the “molecular middleman,” carrying instructions from genes to the protein-building mechanisms of cells, tagging them for destruction.
The team found that when they increased levels of miR-30a-5p in the mPFC, BDNF reduced, prompting the mice to consume large quantities of alcohol.
However, when the team treated the mice with an inhibitor of miR-30a-5p, the BDNF level in the mPFC reverted to normal, and alcohol consumption was likewise normal once again.
Commenting on their findings, Ron says:
”Our results suggest BDNF protects against the transition from moderate to uncontrolled drinking and alcohol use disorders. When there is a breakdown in this protective pathway, however, uncontrolled excessive drinking develops, and microRNAs are a possible mechanism in this breakdown.”
She adds that this mechanism may be the reason “why 10% of the population develop alcohol use disorders,” noting that their study could help in the development of medications to treat AUDs.
Other potential therapies for alcohol problems have been unsuccessful, the researchers say, because they work by inhibiting the brain’s reward pathways, which causes a decrease in how individuals experience pleasure.
However, this latest study demonstrated that the reward pathways still function in mice whose miR-30a-5p had been dialed down, a result that shows potential for future treatments, according to Ron.
“In searching for potential therapies for alcohol abuse,” she says, “it is important that we look for future medications that target drinking without affecting the reward system in general. One problem with current alcohol abuse medications is that patients tend to stop taking them because they interfere with the sense of pleasure.”
The NIAAA note that only a fraction of individuals who could benefit from treatment receive help; in 2012, only 8.4% of adults in need received treatment for an AUD at a specialized facility.
Medical News Today recently reported on a study that suggested alcohol is more likely to induce “social bravery” in men than in women because it heightens sensitivity to rewarding social behaviors for men in particular.