Researchers found unusually high BNST activity in abstinent mice that later showed compulsive-like alcohol drinking.
For some people, a period without alcohol can later be followed by more compulsive drinking. In mice undergoing abstinence, our research team found that changes in the activity of a specific brain region appeared before this compulsive drinking behavior, raising the possibility that similar signals could eventually help identify people especially vulnerable to relapse.
Giving up alcohol is associated with better health outcomes, but addiction researchers have proposed that changes occurring in the brain during abstinence could also increase vulnerability to relapse.
Abstinence can precede compulsive drinking
To explore this theory, we studied how mice behaved after giving them long-term voluntary access to alcohol followed by a forced abstinence period. We found that a subset of the mice developed aversion-resistant alcohol intake – that is, they now drank alcohol despite the quinine we added to make it increasingly bitter. Moreover, compared to those who did not experience forced abstinence, these mice drank even larger quantities of the very bitter alcohol. These results suggest there are potential bodily challenges associated with abstinence that contribute to relapses in alcohol use disorder.
Next, we monitored the activity of a particular collection of cells in a portion of the brain known as the bed nucleus of the stria terminalis, or BNST. Researchers have previously found this small structure to be heavily implicated in alcohol use disorder symptoms such as anxiety and depression.
We found that allowing abstinent mice to reenter the setting where alcohol was previously available would lead them to attempt to drink even though the spout contained only water. These attempts were associated with activity in the BNST. Abstinent mice who had developed the taste for very bitter alcohol had more than double the activity in this brain area compared to mice that did not experience forced abstinence.
Importantly, we saw activity in the BNST even before we gave abstinent mice access to the bitter alcohol. This finding suggests it might be possible to identify people who are at risk of relapsing by screening for BNST activity when someone is given access to alcohol.
Predicting relapse remains a clinical challenge
Alcohol misuse is one of the top public health challenges in the United States. Although this condition is linked to a wide variety of negative health effects, the public chronically underestimates its seriousness.
Deaths associated with alcohol use in 2024 were 4.5 times higher than deaths attributed to opioids. While harm reduction – a major component of opioid use disorder treatment – is being explored in alcohol use disorder, abstinence remains a mainstay of most approaches to this addiction.
Over 80% of Americans age 12 and older consume alcohol at some point in their lives, and around 10% go on to experience alcohol use disorder. This 10% amounts to almost 30 million people in need of treatment.
Unfortunately, clinicians are ill-equipped to predict who will need help. Although there are treatments approved by the Food and Drug Administration for alcohol use disorder, the number of people diagnosed with this condition remains very high. In fact, those numbers have effectively doubled in the U.S. since 1999.
Developing better strategies for identifying those at risk of developing alcohol use disorder and helping them navigate treatment strategies may improve treatment.
The BNST mechanism remains unresolved
It’s not clear the exact role that the BNST area of the brain plays in behavior related to alcohol use disorder. It’s also not clear what drives the increase in activity, or which specific populations of brain cells within the BNST encode this activity. Obtaining these answers could lead to new treatment targets.
New tools in neuroscience have allowed researchers to manipulate the activity of specific neurons in mice brains. Using these strategies, our team is working on understanding the role BNST plays in drinking alcohol despite the harmful consequences.
Our colleague Jennifer Blackford is also 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 further test using the BNST as a screening method in clinical trials.
Reference: “Alcohol abstinence precipitates alcohol seeking and aversion-resistant intake in association with increased BNST activity” by Marie A. Doyle, Hye Jean Yoon, Megan E. Altemus, Anika S. Park, Martha E. Troutman, Laura Grunenkovaite, Danielle N. Adank, Caitlyn M. Edwards, Nia A. Chetkovich, Sabrina D. Hallal, Louise Lantier, Cody A. Siciliano, Erin S. Calipari and Danny G. Winder, 3 June 2026, Molecular Psychiatry.
DOI: 10.1038/s41380-026-03660-x
The work performed by the Vanderbilt Mouse Metabolic Phenotyping Center was supported by grants from the National Institute of Health (U2 DK135073 and P60 DK020593 from NIDDK; P60 AA031124 from NIAAA). Additional grant support from the National Institute of Health was provided as follows.
Adapted from an article originally published in The Conversation.
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