Enzyme Malfunction May Cause Binge Drinking To Lead To Alcoholism

Scientists at the Stanford University School of Medicine have discovered that a malfunctioning enzyme, known as ALDH1a1, may be the reason that binge drinking increases the odds of developing alcoholism.

Previously, the scientists discovered that blocking ALDH1a1 activity in mice caused their consumption and preference for alcohol to rise immensely, to the point where the levels were equal to those found in mice that had gone through several rounds of "binge drinking," according to the study.

This discovery has presented possibilities of creating medications that could diminish the urge to drink alcohol, according to Dr. Jun Ding, a professor of neurosurgery and the senior author of the study.

Currently, medications for alcoholism have had varying results. Many of them cause side effects that are quite unpleasant if the person taking them does consume alcohol, like shortness of breath, nausea, vomiting, and painful headaches.

"But these drugs don't reduce the craving -- you still feel a strong urge to drink," Ding said.

Previous studies showed that mutations in the gene for ALDH1a1 are linked to alcoholism, but scientists were unsure how.

This new study has revealed that in certain nerve cells that are largely involved in addictive behaviors, ALDH1a1 is an important part in a previously unseen biochemical "assembly line" for the manufacture of a neurotransmitter known as GABA, which is the main inhibitory transmitter in the brain. It was previously believed that the manufacture of GABA did not involve ALDH1a1.

GABA is widely produced throughout the brain, but researchers observed the novel production of GABA in a group of nerve cells that play a powerful role in addiction. This means that a drug that could boost the levels of ALDH1a1 could potentially restore the balance in the brain's neural circuitry that has been throw out of balance by alcohol consumption.

Until recently, neuroscientists widely assumed that each type of nerve cell in the brain can only release one neurotransmitter. But in 2012, Ding discovered that dopamine-producing nerve cells, can also produce and release other types of neurotransmitters as well, including GABA. These dopamine-producing nerve cells supercharge the brain's reward-inducing behavior, playing a huge role in addiction. Additionally, these cells not only produce both dopamine and GABA, but release them simultaneously, according to the release.

"All of us normally encounter countless reward-inducing situations without getting addicted," Ding said. "Every time I publish a paper, my dopamine-producing nerve cells go crazy, but I don't get addicted. Why not?"

In the study, the team used advanced methods to impair ALDH1a1 activity in the mice, and the result was shocking. GABA levels in dopamine-producing nerve cells dropped in the same fashion that they did when mice with normal ALDH1a1 activity participated in binge drinking. When ALDH1a1 levels were raised, the effects were reversed. 

Alcoholism currently affects more than 200 million people globally, including 18 million Americans. Binge drinking substantially increases the likelihood of developing alcoholism, and up to one in four American adults report having engaged in binge drinking in the past month. 

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