New Clues to Why Addiction Persists
A groundbreaking study from Scripps Research has uncovered how a specific brain region drives alcohol addiction by linking drinking behavior to relief from withdrawal pain. The findings, published on August 5, 2025, in Biological Psychiatry: Global Open Science, identify the paraventricular nucleus of the thalamus (PVT) as a key site where the brain learns to associate alcohol with relief from stress and anxiety. The discovery could pave the way for new therapies to treat substance use disorders (SUDs) and related conditions such as anxiety and trauma-related behaviors.
Researchers found that when rats experienced withdrawal and then consumed alcohol, the PVT became highly active, reinforcing the behavior of drinking to escape discomfort rather than to experience pleasure. This mechanism may explain why relapse is so persistent among people recovering from alcohol dependence.
How the Brain Learns Addiction
An estimated 14.5 million Americans suffer from alcohol use disorder, which involves repeated cycles of withdrawal and relapse. The Scripps team, led by neuroscientists Friedbert Weiss and Hermina Nedelescu, used animal models to explore how the brain encodes the motivation to drink. They discovered that rats who learned that alcohol relieved withdrawal stress were far more likely to seek it out again, even when faced with punishment or obstacles.
“When rats learn that alcohol relieves the unpleasant feelings of withdrawal, they develop an extremely strong urge to seek it out,” explained Weiss. “They continue even when it’s difficult or costly to do so.” Nedelescu added that brain scans showed the PVT “lighting up” in every rat that had learned this behavior, underscoring its central role in addiction learning.
The Paraventricular Nucleus and Negative Reinforcement
Using advanced whole-brain imaging, the researchers compared activity across different groups of rats—those with withdrawal experience and those without. Only the withdrawal-trained group showed significantly elevated activity in the PVT, an area already known for its involvement in stress and emotional regulation. This suggests that the thalamic region helps encode the connection between alcohol and relief from negative emotions, reinforcing relapse-driven behavior.
“The unpleasant effects of alcohol withdrawal are strongly tied to stress,” Nedelescu said. “The PVT appears to process that connection, helping the brain link alcohol use to relief from that stress.” This process, known as negative reinforcement, helps explain why people often relapse not to feel good, but to stop feeling bad.
Broader Implications for Addiction Treatment
The study’s insights extend beyond alcohol use disorder. The same neural mechanisms that drive the urge to escape pain or fear may also underlie other conditions such as anxiety, compulsive behavior, and post-traumatic stress disorder. “This work has potential applications not only for alcohol addiction, but also for disorders where people get trapped in harmful cycles,” said Nedelescu.
Future research will expand to include female subjects and examine the neurochemicals released in the PVT during withdrawal-related experiences. By identifying specific molecules involved in this brain process, scientists hope to develop targeted drugs that could disrupt the cycle of negative reinforcement and reduce relapse rates.
“As psychologists, we’ve long known that addiction isn’t just about chasing pleasure—it’s about escaping pain,” said Weiss. “Now we’re beginning to see where in the brain that learning takes root, and that represents real progress in understanding and treating addiction.”