Mouse Study Links Abstinence-Related Brain Activity to Alcohol Relapse Risk

Addiction researchers have long theorized that brain changes occurring during abstinence from alcohol may increase a person's risk of relapse. To test this, researchers gave mice long-term voluntary access to alcohol, followed by a period of forced abstinence. A subset of the abstinent mice went on to develop what the researchers call 'aversion-resistant alcohol intake': they kept drinking alcohol even after quinine was added to make it increasingly bitter, and they drank larger quantities of the bitter alcohol than mice that had not gone through forced abstinence.

The researchers then monitored activity in the bed nucleus of the stria terminalis (BNST), a small brain structure previously linked to alcohol use disorder symptoms such as anxiety and depression. When abstinent mice were returned to the setting where alcohol had previously been available, they attempted to drink even though the spout now contained only water, and these attempts were associated with BNST activity. Abstinent mice that had developed a taste for very bitter alcohol showed more than double the BNST activity of mice that had not experienced forced abstinence, and this heightened activity appeared even before the mice were given access to the bitter alcohol, suggesting BNST activity could help identify people at risk of relapse.

Alcohol misuse is one of the top public health challenges in the United States, the researchers said, and the public chronically underestimates its seriousness. Alcohol-related deaths in 2024 were 4.5 times higher than deaths attributed to opioids. More than 80% of Americans aged 12 and older consume alcohol at some point in their lives, and about 10% go on to experience alcohol use disorder, amounting to almost 30 million people in need of treatment. Although the FDA has approved treatments for alcohol use disorder, diagnoses have roughly doubled in the U.S. since 1999.

It remains unclear exactly what role the BNST plays in alcohol use disorder behavior, what drives the increase in its activity, or which specific populations of brain cells within it encode that activity, the researchers said.

The team is now using tools that let researchers manipulate the activity of specific neurons in mice brains to further study the BNST's role in drinking despite harmful consequences. A colleague, Jennifer Blackford, is separately investigating BNST activity in the brains of people with alcohol use disorder who are in early abstinence; if her team observes similar findings in people, a next step would be to test the BNST as a screening method in clinical trials.