Mouse Study Finds Brain Target to Block Alcohol Cravings

For folks who have battled alcohol dependency for years, any treatment that could curb or block alcohol cravings would be a huge advance.

Now, research in mice is giving a glimmer of hope that just such a therapy might be possible.

A compound — so far dubbed LY2444296 — appears to block a key brain cell receptor called the kappa opioid receptor (KOP), a team at the Scripps Research Institute in California reports.

“Compounds designed to selectively block the KOP are very promising because this receptor is involved in a lot of mental illnesses, such as anxiety and depression,” said senior study author Rémi Martin-Fardon, an associate professor of molecular medicine at Scripps.

“The KOP system is also important in alcohol use disorder, so the idea is if it’s targeted and blocked, you can stop alcohol abuse,” he explained in a Scripps news release.

However, this research has so far only been conducted in mice. Experts are quick to point out that many findings seen in animals are not replicated in humans, and further study is needed.

The new study was published recently in the journal Scientific Reports.

Martin-Fardon’s team knew that the brain’s “KOP system” helps direct a range of brain responses including addiction, emotion, pain and reward-seeking. Alcohol intake can negatively affect KOP, as well.

In the study, the Scripps team tested the new compound on mice that had become alcohol-dependent. Would LY2444296 ease their cravings?

The rodents were given relatively low doses of LY2444296 about 8 hours after they’d last received alcohol — about the same interval for when serious withdrawal symptoms begin to emerge in people.

Behaviors of alcohol withdrawal normally exhibited by mice “tapered down significantly,” according to the news release.

The fact that LY2444296 acted in such a a short time was surprising to Martin-Fardon’s team, since prior agents used to block KOP seemed to have no impact on alcohol withdrawal, they said.

The exact reasons behind LY2444296’s effects remain unclear.

“People drink to get rid of the sensations of withdrawal,” Martin-Fardon said, and for most, “the only thing that can fix the problem is to have a drink.”

Perhaps, if LY2444296 is taken before withdrawal symptoms begin, “you can decrease the symptoms, so you feel better and drink less,” he reasoned.

The research still has far to go, however. Right now, the Scripps team don’t know which parts of the brain to target to maximize any benefit from LY2444296. They also want to be understand the compound’s stress-reducing effects.

“We’re also interested in what brain regions are changing as a function of alcohol dependence,” said study lead author Francisco Flores-Ramirez, a postdoctoral fellow at Scripps. “Maybe we could target them to see if the compound could reverse both drinking and relapse behavior.”

In mice anyway, LY2444296 appeared to have no ill effects, even when used in those without alcohol dependency, the team noted.

More information

Find out more about alcohol and the brain at the National Institute on Alcohol and Alcoholism.

SOURCE: Scripps Research Institute, news release, March 29, 2024