A newly explored part of the brain controls our ability to avoid negative alcohol experiences.

Most of the research done on alcohol addiction so far has focused on the rewarding effects of alcohol. It offers euphoria, boosts mood if someone is feeling depressed, and soothes fear if someone is feeling anxious. But new research has found another important component of developing a substance-abuse problem: the inability to learn from the consequences of drinking too much.

The study, published in PLOS One, examined a region of the brain called the lateral habenula. Previous research had found that the lateral habenula is associated with making decisions and learning about punishments.

“Neurons in this brain region are responsive to outcomes that are negative,” said Sharif Taha, assistant professor of neurobiology and anatomy at the University of Utah School of Medicine and the study’s principal investigator, in an interview with Healthline. “A negative outcome could be something like a painful stimulus, or it could be some outcome that was worse than you expected. So, if you press a button on a vending machine and you’re expecting to get a candy bar and you don’t get it, then your lateral habenula neurons are probably activated. The habenula is important to associate that action with the lack of the outcome that you wanted so you can avoid it in the future.”

In this study, the scientists destroyed the lateral habenula of rats, and then measured how their behaviors changed.

In the first experiment, the team gave each rat two water bottles: One bottle contained clean water, and the other one contained water with 20 percent alcohol—the equivalent of 40-proof drink. The rats could choose to drink as much water from either bottle as they pleased. The rats with the damaged lateral habenulae, escalated their alcohol consumption more rapidly, and they drank greater amounts of alcohol overall.

In another experiment, the scientists let the rats drink highly desirable sugar water, and then injected them with a strong dose of alcohol to make them feel sick. As with humans, alcohol appeared to make the rats sleepy, nauseated, and uncoordinated. The normal rats disliked this sensation and learned to avoid the sugary mixture, while the rats with lesioned lateral habenulae kept drinking it.

“We think that what the habenula is contributing is some learning about ‘How bad was my last drinking session? Maybe I should curb my next drinking session. I’m not going to escalate,’” said Taha. “The rats that don’t have habenula activity are the ones which go up and up and up over time. Either they’re just not experiencing those aversive effects, or they’re not learning from them.”

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In this theory, the pathway to addiction is a careful balance—if someone finds alcohol too rewarding, and its overuse not punishing enough, then they have an incentive to keep drinking and no reason to stop.

“It seems that it’s not just the rewarding effects that are important in determining how motivated someone might be to consume alcohol, it’s also whether or not they experience any of these aversive effects,” Taha said. “That may play a role in, over time, whether you’re content to consume a couple of beers, or if you’re someone who escalates over time.”

Gantt Galloway, senior scientist in the Addiction & Pharmacology Research Laboratory at the California Pacific Medical Center Research Institute in San Francisco, hopes to see more work on how the lateral habenula works in humans.

“If there are differences in lateral habenula function in people, then what’s the basis for those differences? Are those differences genetic, and can one then identify a [genetic profile] that’s associated with increased risk for alcoholism?” he said. “That could be a useful predictive diagnostic test and could conceivably predict who’s going to respond to different sorts of treatments as well.”

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More than 50 percent of alcoholism can be accounted for by genetic factors, which might govern the growth of brain regions such as the lateral habenula and the areas associated with reward. But Galloway warns that brains, rats, and people can’t be examined in a void, especially when it comes to drug use.

He explained that addiction is often a matter of alternative reinforcers—that is to say, positive things to do with one’s time other than use drugs.

“Whether one is going to use drugs or not is a choice based on what the alternative reinforcers are,” he said. “If you have nothing else to do and life is not very pleasant, if you are a social creature—for example, a rat, and you are solo-housed in a boring environment as rats are generally housed for experiments, in that setting it is very easy to get animals to self-administer drugs. If one has them in an enriched environment in which they can socialize, have sex, groom, all those things that rats like to do, then it’s much more difficult to get them to self-administer drugs. It’s much more difficult to induce something that looks like an animal model of addiction.”

It’s a fair bet that if humans were forced to live in the same conditions as the rats in Taha’s experiment—alone, in a tiny cage, with nothing to do—and given unlimited access to drugs, they might pass the time by using drugs, too.

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Brain wiring partly determines who is vulnerable to alcoholism. A lack of self-control at a young age—which is measurable by evaluating a child’s response after asking whether the youngster wants one candy now or two candies later—is also a predictor of substance-abuse problems, as well as other problems, later in life. Mental illness also leaves people vulnerable to alcohol abuse.

“People may use alcohol to relieve negative symptoms if they do not like their mental state,” Galloway said. “For example, if they have a history of trauma, of PTSD [post-traumatic stress disorder], they may use alcohol or other drugs to try to avoid symptoms.”

Other physical factors are also at play. For example, because of differences in liver enzymes, men have a higher alcohol tolerance than women, putting males at greater risk for alcoholism.

Race also comes into the equation. People of Asian ancestry often lack an alcohol-digestion enzyme common among Europeans, causing them to experience more undesired side effects, such as nausea and flushing, and making them less likely to develop alcoholism. Native Americans, on the other hand, metabolize alcohol more slowly than Europeans, allowing them to drink more before feeling its negative effects. This places them at higher risk.

But the rest of the picture comes from the environment, especially relationships with people. Here, a heavy load of risk factors and a lack of protective factors can tip the scales toward substance abuse. Growing up in poverty, living in a violent household, having weak ties to family and community, being brought up by inattentive parents, and feeling social pressure also contribute to person’s likelihood of abusing alcohol.

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