Drinking triggers brain changes that teach you to want more alcohol, Penn researchers find

Running into a former drinking buddy or passing a once-favorite bar can cause recovering alcoholics to relapse.

But the biology behind why those setbacks happen was a mystery to scientists until recently, when researchers from the Perelman School of Medicine at the University of Pennsylvania found that alcohol directly affects the brain’s learning and memory system through a test on mice.

Drinking actually helps people’s brains “learn” alcohol ⁠— the bar they’re drinking in, the street they’re on, and the people they’re with ⁠— said Shelley Berger, a cell and developmental biology professor who is the study’s senior author. This learning can make people want to drink more when they’re in certain environments or with groups of people.

And unraveling how the learning happens opens the possibility someday of treatments to block the action.

Berger’s research is the latest addition to a growing body of research that alcohol and drugs can cause genetic changes that may reinforce addiction and affect future generations. Earlier this year, researchers from Rutgers University found that binge drinking can trigger genetic changes that make people crave alcohol even more.

In the new study, published Wednesday in the journal Nature, researchers found that when alcohol is consumed, it goes to the liver, where it’s processed into acetate, a byproduct. Acetate then travels to the brain, where it turns certain genes on and off in a cell by attaching to histones, the proteins that package DNA in a cell’s nucleus, Berger said.

“DNA is about two feet long in every cell and it’s all folded up into the nucleus,” she said. “There’s a packaging material that organizes it in a really orderly way, and it turns the right genes on and off through these little chemical groups. Acetate is one of those chemical groups.”

It turns out that the enzyme responsible for depositing acetate into cells, called ACSS2, activates key memory genes important for learning.

To test this, researchers exposed mice to two differently patterned chambers ⁠— one with alcohol and one without. After a “learning period,” the mice were allowed to roam freely between the two. They preferred the chamber that was paired with alcohol.

But after lowering the levels of ACSS2 in the mice’s brains, researchers found that they spent an equal amount of time in both chambers.

Researchers also found that when a pregnant mouse consumed alcohol, acetate was delivered through the placenta and into the fetus’ developing brain. This finding could lead to better understanding of fetal alcohol syndrome, said Berger.

Berger said that this was the first empirical evidence showing that alcohol consumption affects how genes are expressed in the brain. She’s now interested in using the information to make a drug that could be used to stop people from “learning” alcohol.

“When we learn something, there’s a process called reconsolidation,” Berger said. “That’s when something is really solidified, and we feel that we really understand it now. We want to disrupt that, after someone has been exposed to alcohol but before they reconsolidate the information.”

Henry Kranzler, the director of Penn’s Center for Studies on Addiction, said Berger’s research is “intriguing" because it offers the potential of “filling in a missing piece in our understanding of the development and maintenance of heavy drinking."

“Her research is consistent with the idea that addiction is a learned process,” he said. “Importantly, it opens up the potential to identify specific targets in the brain to be modified therapeutically with medications and perhaps also genetically, at some point.”

In other words, researchers can make drugs to treat addiction that target specific areas of the brain that are affected by alcohol.

However, the next step is to conduct more research using animals before eventually moving on to humans.

“This is a really exciting, unexpected finding, that alcohol consumed would end up in the brain,” Berger said. “What this tells us is that acetate may be a very good thing for memory, but a lot might not be good, especially if you’re getting it in the context of something that’s not good for you.”