Anyone who’s been part of a rowdy New Year’s celebration knows that a little alcohol can make us euphoric, energetic, and affectionate. But the more we drink, the more we descend into a (sometimes life-threatening) stupor. The scientists behind a recent study claim to have worked out how that initial buzzed feeling happens, all thanks to some drunk-as-hell fruit flies.
The study, published this month in Journal of Molecular Biology, comes courtesy of scientists at Scripps Research Institute, a non-profit research center and graduate school based in California and Florida.
Based on earlier research, the team theorized that alcohol’s drowsy effects on the brain were similar to those of anesthesia. So they decided to closely study a molecular pathway activated in nerve cells when we drink alcohol or undergo sedation, involving the enzyme phospholipase D2, or PLD2. PLD2 is thought to help connect ethanol molecules to the fat stored in the membrane, or surface, of nerve cells. And they used fruit flies as a placeholder for people because flies remarkably seem to behave like we do when they imbibe.
“They act just like people,” senior author Scott Hansen, an associate professor in the Department of Molecular Medicine at Scripps, said in a statement. “They start losing coordination. They literally get drunk.”
Hansen and his team placed flies in a small tube and fed them liquid food dosed with alcohol, and the flies predictably became buzzed. When they looked at the brains of these flies afterward, they found that the activation of PLD2 via alcohol led to a chain reaction of other processes inside nerve cells. Specifically, PLD2 breaks down alcohol into other molecules, or metabolites, and one of these metabolites is a molecule made of both fat and alcohol called phosphatidylethanol (PEtOH). The accumulation of PEtOH in turn seems to goad nerve cells into firing more easily, meaning their brains become hyperactive.
“With hyperactivity you see the flies run around more, and this is what we equate to being buzzed,” Hansen explained.
Hansen and his team also created flies that had the gene that let their brain cells recognize PLD2 turned off. These flies, unlike the unaltered flies, didn’t act buzzed at all, supporting their case that PLD2 plays a pivotal role in creating the initial buzzed feeling of being drunk.
The findings are especially interesting, the authors say, because alcohol is largely thought to affect brain cells directly. But this would be an example of the drug indirectly affecting cells, through the PLD2 pathway. That’s important because we’re obviously interested in being able to stop the worst effects of alcohol in people. So it’s possible drugs that can someday safely interact with PLD2 can stop us from getting drunk in the first place—which could help people dealing with alcohol dependence. Maybe stopping PLD2 might even prevent other negative aspects of drinking, like a brutal hangover.
“It has definitely led to some different ways of thinking about alcohol intoxication at the molecular level,” Hansen said. “Most scientists thought alcohol had a direct effect. Blocking the enzyme in flies shows that’s not likely true.”
Fruit flies are a handy substitute for people, but of course, their brains aren’t quite like ours. So there’s lot of more work needed to figure out whether PLD2 is a key player in getting humans buzzed, too. Hansen and his team also plan to keep studying just how important PLD2 is in helping create the other notorious effects of alcohol, including sedation.
[Journal of Molecular Biology via Scripps]
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