Addiction researchers have theorized that brain changes occurring during alcohol abstinence may increase relapse risk, a hypothesis recently explored through a study on mice given long-term voluntary access to alcohol followed by a forced abstinence period as reported by ScienceDaily. The study observed that a subset of mice developed aversion-resistant alcohol intake, continuing to drink alcohol despite the addition of quinine to make it increasingly bitter. Furthermore, these mice drank even larger quantities of the bitter alcohol compared to counterparts that did not undergo forced abstinence.
Brain Changes During Alcohol Abstinence Linked to Relapse Risk in Mice
Researchers monitoring brain activity focused on a small structure known as the bed nucleus of the stria terminalis, or BNST, which is located deep in the center of the brain as noted by The Independent. This specific brain region has previously been implicated in alcohol use disorder symptoms such as anxiety and depression. When abstinent mice were allowed to reenter the setting where alcohol was previously available, they attempted to drink even though the spout contained only water, and these attempts were linked to activity in the BNST. Abstinent mice that developed a taste for very bitter alcohol exhibited more than double the activity in this brain area compared to mice without forced abstinence. Crucially, researchers detected activity in the BNST even before granting the abstinent mice access to the bitter alcohol.
Public Health Stakes and Current Treatment Landscape
Alcohol misuse remains a major public health challenge in the United States, although 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 serves as a major component of opioid use disorder treatment and is being explored in alcohol use disorder, abstinence remains a mainstay of most approaches to this addiction.
Demographic data indicates that 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% figure amounts to nearly 30 million people in need of treatment. Despite Food and Drug Administration-approved treatments being available for alcohol use disorder, the number of diagnosed individuals remains very high and has effectively doubled in the U.S. since 1999. Clinicians currently remain ill-equipped to predict who will require help, highlighting the need to develop better strategies for identifying at-risk individuals and helping them navigate treatment.
Unresolved Questions and Future Research Directions
Despite the findings connecting BNST activity to relapse-related behaviors, several questions remain open. It is not yet clear what exact role the BNST area of the brain plays in behavior related to alcohol use disorder. Additionally, researchers do not yet know what drives the increase in activity, nor which specific populations of brain cells within the BNST encode this activity. Obtaining answers to these questions could lead to the identification of new treatment targets.
To build on these discoveries, researchers are utilizing new neuroscience tools to manipulate the activity of specific neurons in mouse brains to better understand the role the BNST plays in drinking alcohol despite harmful consequences. Meanwhile, colleague Jennifer Blackford is investigating BNST activity in the brains of humans with alcohol use disorder who are in early abstinence. Should her team observe similar findings in people, a planned next step involves further testing the BNST as a screening method in clinical trials.
