New research suggests that quitting alcohol may lead to brain changes that could increase the risk of relapse. Scientists have long suspected that the brain adapts during periods of abstinence from alcohol, which might make it harder for some people to stay sober. To study this, researchers looked at mice that had access to alcohol over a long period and then went through a forced abstinence phase. Some of these mice developed a resistance to the bitter taste of alcohol, even when quinine—a substance that makes alcohol taste bitter—was added. These mice drank more of the bitter alcohol than those that didn’t go through the abstinence period. The study focused on a part of the brain called the bed nucleus of the stria terminalis (BNST), which is known to be involved in emotions like anxiety and depression. Researchers found that mice that had been abstinent showed increased activity in the BNST when they were given access to water instead of alcohol. Mice that had developed a preference for bitter alcohol had more than twice the BNST activity compared to those without forced abstinence. This increased activity was observed even before the mice were given access to the bitter alcohol, suggesting that BNST activity might be used to identify people at higher risk of relapse. Alcohol misuse is a major public health issue in the United States. In 2024, deaths related to alcohol use were nearly five times higher than those linked to opioids. While various strategies are being explored to reduce the harm caused by alcohol use, abstinence remains a common treatment approach. Over 80% of Americans age 12 and older drink alcohol at some point in their lives, and about 10% develop alcohol use disorder, affecting nearly 30 million people who need treatment. However, healthcare providers currently lack tools to predict who will need help, and the number of people diagnosed with alcohol use disorder has more than doubled in the U.S. since 1999. The role of the BNST in alcohol use disorder and the specific brain cells involved are still not fully understood. Researchers are using new tools in neuroscience to manipulate specific neurons in mice to better understand how the BNST influences drinking behavior despite negative consequences. Meanwhile, a colleague, Jennifer Blackford, is studying BNST activity in humans with alcohol use disorder during early abstinence. If similar results are found in people, it could lead to clinical trials exploring BNST activity as a potential screening method for relapse risk.