Scientists discover brain circuit driving alcohol addiction relapse
Researchers at Scripps Research have identified a brain region that becomes hyperactive in rats, linking alcohol to relief from withdrawal stress and promoting relapse. The paraventricular nucleus of the thalamus plays a key role in this negative reinforcement learning. The findings, published on August 5, 2025, could inform treatments for addiction and related disorders.
A new study from Scripps Research reveals how a specific brain circuit traps individuals in alcohol addiction by associating the substance with escape from withdrawal discomfort. Published in Biological Psychiatry: Global Open Science on August 5, 2025, the research focused on the paraventricular nucleus of the thalamus (PVT) in rats. This midline brain region showed heightened activity when rats learned to link environmental cues with alcohol's ability to ease withdrawal symptoms, driving persistent relapse behavior.
The team, led by senior authors Friedbert Weiss, professor of neuroscience at Scripps Research, and Hermina Nedelescu, compared four groups of rats using advanced brain imaging. Only those exposed to withdrawal and conditioned to seek alcohol for relief exhibited strong PVT activation. "What makes addiction so hard to break is that people aren't simply chasing a high," Weiss explained. "They're also trying to get rid of powerful negative states, like the stress and anxiety of withdrawal."
This builds on 2022 work by Weiss and Nedelescu, which examined learning cycles in alcohol use disorder affecting an estimated 14.5 million Americans. Initial drinking reinforces pleasure-seeking, but repeated withdrawal intensifies negative reinforcement, making relapse more stubborn—even under punishment. "This brain region just lit up in every rat that had gone through withdrawal-related learning," Nedelescu noted. "It shows us which circuits are recruited when the brain links alcohol with relief from stress."
The PVT's role aligns with its known involvement in stress and anxiety, explaining why withdrawal's agony strengthens addiction. Beyond alcohol, the mechanism may apply to anxiety disorders and trauma avoidance. Future studies will explore female rats and neurochemicals in the PVT to target new therapies. Co-authors include Elias Meamari, Nami Rajaei, and others, with funding from the National Institutes of Health.