Competing memories in the brain drive relapse and recovery from alcohol addiction – Texas A&M Stories

Every experience leaves a trace in the brain, a memory that can shape future behavior. Alcohol and other addictive substances are no exception. Over time, repeated alcohol use can create strong memories that link certain places, cues or actions with reward. These memories can persist even after a person stops drinking, making relapse a common and ongoing challenge for the treatment of alcohol use disorder.

New research from the Texas A&M University Naresh K. Vashisht College of Medicine at Texas A&M Health is helping to explain why this happens and may offer new clues for developing more effective treatments.

A study from the lab of Jun Wang, professor in the Department of Neuroscience and Experimental Therapeutics, discovered that the brain stores competing alcohol-related memories in different groups of the same type of brain cell within a single brain region. The findings suggest that the brain keeps both the memory that drives relapse and the memory that helps suppress it, allowing the two to exist side by side and compete for control over behavior.

The study, led by Xueyi Xie, a postdoctoral research associate in Wang’s lab, examined how alcohol-related experiences create long-lasting memories that drive alcohol-seeking behaviors. Treatments like extinction training are designed to reduce alcohol seeking and relapse by repeatedly exposing individuals to alcohol-related cues or behaviors without the alcohol reward. However, scientists do not fully understand how these treatments work in the brain, and their long-term success has remained limited.

“Relapse is driven in part by long-lasting memories formed during alcohol use, and treatments like extinction training are often thought to weaken or replace those memories,” Xie said. “But our findings suggest the original memory may still remain, while a second, competing extinction memory forms alongside it. This points to the idea that strengthening the extinction memory may offer a new direction for improving addiction treatment.”

In the study, subjects first learned to press a lever to receive alcohol. They then underwent extinction training, in which pressing the lever no longer delivered alcohol, causing alcohol-seeking behavior to gradually decline. To see what was happening in the brain, the researchers examined activity in the dorsomedial striatum, a region involved in decision making and goal-directed behavior. They found that alcohol use and extinction training activated two groups of the same kind of brain cell. One group, activated during alcohol use, encoded a memory that promoted alcohol seeking and relapse. The other, activated during extinction training, encoded a memory that suppressed alcohol seeking and opposed relapse. Each group formed a distinct “engram,” or network of brain cells that stores a specific memory.

“An engram is essentially the brain’s physical record of a memory,” Wang said. “By identifying these memory-carrying cells, we can begin to understand how relapse and recovery are controlled in the brain.”

The team also found important differences between the two groups of cells. Cells linked to relapse were spread broadly across the dorsomedial striatum and were associated with behavioral reinforcement. In contrast, extinction-related cells were concentrated in specialized compartments called striosomes, which are associated with behavioral inhibition.

To test whether these memory-related cell groups actually control behavior, the researchers selectively activated or inhibited each group. They found that manipulating these cells could either increase or decrease alcohol-seeking behavior, showing that the two groups have opposite effects on relapse.

The researchers also looked at the connections between brain cells, called synapses. They found that relapse-related memories were stored in strengthened communication between the medial prefrontal cortex and striatal neurons. Because the brain stores memories through changes in these connections, this finding shows that relapse-related memories have a physical basis in specific brain circuits. When the researchers artificially recreated this strengthening, they were able to trigger relapse-like behavior, even without prior alcohol exposure.

“These findings show that relapse-related memories are built into specific brain connections,” Wang said. “By understanding how these connections change, we can begin to think about ways to weaken the circuits that drive relapse or strengthen those that support recovery.”

The findings suggest that addiction is shaped by a balance between competing neural systems — one that promotes relapse and another that suppresses it. Rather than erasing harmful memories, extinction training appears to build a new memory that must actively compete with the original one.

“This work gives us a new way to think about relapse, not simply as the return of a single memory, but as the outcome of competing processes in the brain,” Wang said. “By understanding this balance, we may be able to develop more targeted strategies to reduce relapse risk.”

By identifying the specific cells and connections involved in these opposing memory processes, the study offers a potential roadmap for more precise interventions. Future treatments could focus on weakening circuits associated with relapse or strengthening those that support recovery, the researchers said.

As scientists continue to uncover the brain basis of addiction, this work offers new insight into how the brain encodes both vulnerability and resilience and how that balance might be shifted to improve long-term outcomes.

This research was supported by the funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA/NIH; U01AA025932, R01AA027768, and R01030293).