Fruit Flies Reveal the Neurological Roots of Alcohol Tolerance, Study Shows

Drinking has some confusing effects. It can make you friendlier and less inhibited, but it can also make you aggressive; it can cause total blackouts, but it can also improve memory. And for some people with a high tolerance, alcohol doesn’t seem to do anything. In a paper published Monday in the journal eNeuro, neurobiologists explain how alcohol tolerance might develop in the first place.

As anyone with an uncanny ability to crush a case of beers without passing out illustrates, alcohol tolerance is the body’s ability to withstand the normal effects of alcohol. The most obvious mark of tolerance is increased alcohol consumption, which is observed in humans as well as fruit flies, as the new paper shows. By observing the brains of drunk flies, the authors of the paper demonstrate that alcohol tolerance could be a result of the way ethanol acts on a specific group of proteins — the Unc13 family — in the brain. In the study, the flies whose Unc13 proteins were affected by alcohol drank more alcohol than normal flies.

The Unc13 proteins influence the way neurotransmitters — the brain’s signaling molecules — move between neurons, and it appears that their ability to send those signals is strongly affected by alcohol. In previous research, the study’s authors found that fruit flies that had been genetically altered to have reduced Unc13 activity drank more alcohol than unaltered flies; the implication was that Unc13 mediates intoxication and that having less Unc13 activity made flies act like people with high tolerance. In the new study, the team investigated how alcohol affects Unc13 in the first place and, sure enough, found alcohol changes the proteins in a way that increases alcohol tolerance.

When alcohol binds to the Unc13 proteins, they write, it inhibits the binding of another molecule called diacylglycerol, which is also crucial to brain signaling. In other words, intoxicating levels of alcohol reduce the ability of neurons to communicate with each other about how intoxicated the body really is, which, in turn, makes it so that more alcohol becomes necessary to achieve the same intoxicating effects. Alcohol, it seems, has a cyclical effect on tolerance in fruit flies: The more they drink, the more their neurobiology changes, and the more their neurobiology changes, the more they need to drink.

While this study was performed on fruit flies only, it sheds some light on the neurobiology of alcohol tolerance more generally. Currently, scientists are aware of certain conditions that make the development of tolerance more likely, but it’s not clear how it manifests in the brain; knowing that it affects brain signaling related to intoxication is a small but significant step in the right direction. Tolerance is a surprisingly little-studied phenomenon, considering how long humans have been drinking and how serious of a public health issue alcohol addiction has become.

Since we share a lot of genetic similarities with fruit flies, it’s possible that the same effects occur in humans who regularly binge drink. By better understanding the neurobiology of alcohol dependence and tolerance, researchers could shed light on possible treatments for people who live with alcohol dependency.