A new study at the University of North Carolina at Chapel Hill has discovered a surprising new mechanism in the brain that may explain why people recovering from drug addiction often relapse.
Repeated drug use changes the brain in lasting ways. Using a rodent model of cocaine use, UNC researchers found that during abstinence, the brain's immune cells, called microglia, begin actively pruning parts of other support cells known as astrocytes. This damage increased drug-seeking behavior, but when scientists blocked microglia from removing astrocyte pieces, relapse behaviors were reduced.
"Our findings reveal that brain immune cells can drive drug craving by stripping away support structures that help keep neural circuits balanced," said Kathryn Reissner, lead investigator and professor in the department of psychology and neuroscience at UNC-Chapel Hill. "By protecting these connections, we may be able to reduce relapse risk in people recovering from addiction."
Astrocytes are critical cells that help regulate the brain's reward system. Past studies had shown that these cells shrink after cocaine use, but the cause was unknown. This study is the first to demonstrate that the brain's immune system is responsible and that this process directly contributes to relapse risk.
"Addiction treatments have long focused on neurons, but this work shows that targeting the brain's immune system could open an entirely new front in the fight against addiction and relapse," said Anze Testen, co-lead researcher and former graduate student at UNC-Chapel Hill. "It's a promising step toward therapies that preserve brain health during recovery."
The team says the findings could help reshape how addiction is treated in the future. Instead of focusing solely on neurons, treatments may one day aim to protect astrocytes and limit harmful immune responses in the brain.
"This is an exciting example of how basic science can uncover hidden mechanisms of disease," said Jonathan VanRyzin, co-lead researcher and postdoctoral researcher at UNC-Chapel Hill. "By understanding how microglia and astrocytes interact after drug use, we're closer to designing targeted strategies to help people stay drug-free."
Beyond cocaine use, the study highlights a broader principle: neuroimmune interactions may play a key role in how the brain adapts after substance use. The researchers plan to explore whether similar processes occur in humans with substance use disorders.
Tania Bellinger, co-lead researcher and graduate student at UNC-Chapel Hill, added that this work opens up a new set of molecular targets, "Future therapies may be able to block the brain's immune system from pruning healthy cells, ultimately helping people maintain recovery."
The study is available online in the journal Cell Report at: https://www.sciencedirect.com/science/article/pii/S2211124725009088?via%3Dihub
