Cocaine Alters Brain, Fueling Relapse

New research finds cocaine changes how the hippocampus functions, contributing to the ongoing compulsion to seek out the drug.

Published on Mar. 5, 2026

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A new study from Michigan State University researchers has found that cocaine addiction is driven by biological changes in the brain, rather than just personal failure. The researchers discovered that cocaine alters the function of the hippocampus, the brain's memory hub, by increasing levels of a protein called DeltaFosB. This protein acts as a switch, turning genes on and off in the circuit between the brain's reward center and the hippocampus, leading to compulsive drug-seeking behavior. The findings could help scientists develop new pharmaceutical therapies to treat cocaine addiction, which currently has no FDA-approved medications.

Why it matters

Addiction is a complex disease that affects the brain, and this research provides important insights into the biological mechanisms that drive cocaine addiction and relapse. Understanding the role of DeltaFosB and other genes in the brain's reward and memory circuits could lead to more effective treatments for the over 1 million Americans struggling with cocaine addiction.

The details

The study, published in Science Advances and supported by the National Institutes of Health, used specialized CRISPR technology to examine the role of DeltaFosB in the brains of mice exposed to cocaine. The researchers found that this protein acts as a switch, turning genes on and off in the circuit between the brain's reward center and the hippocampus. The longer someone uses cocaine, the more DeltaFosB accumulates in this circuit, altering how the neurons function and leading to a strong drive to seek out the drug. The researchers also identified another gene, calreticulin, that is controlled by DeltaFosB and helps regulate neuron communication, further fueling compulsive cocaine-seeking behavior.

  • The study was published on March 5, 2026.

The players

A.J. Robison

A professor of neuroscience and physiology at Michigan State University and the senior author of the study.

Andrew Eagle

The lead author of the paper and a former postdoctoral researcher in Robison's lab.

National Institutes of Health

The government agency that provided funding for the research.

University of Texas Medical Branch in Galveston

The institution that is partnering with Robison's lab to develop compounds that target DeltaFosB as potential treatments for cocaine addiction.

National Institute of Drug Abuse

The government agency that has provided a grant to Robison's lab and the University of Texas Medical Branch to develop and test compounds that regulate DeltaFosB's ability to bind to DNA.

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What they’re saying

“Addiction is a disease in the same sense as cancer. We need to find better treatments and help people who are addicted in the same sense that we need to find cures for cancer.”

— A.J. Robison, Professor of neuroscience and physiology

“This protein isn't just associated with these changes, it is necessary for them. Without it, cocaine does not produce the same changes in brain activity or the same strong drive to seek out the drug.”

— Andrew Eagle, Former postdoctoral researcher

“If we could find the right kind of compound that works in the right way, that could potentially be a treatment for cocaine addiction. That's years away, but that's the long-term goal.”

— A.J. Robison, Professor of neuroscience and physiology

What’s next

Robison's lab will next examine how hormones impact the brain circuits involved in cocaine addiction and whether cocaine affects the male and female brain differently. This work could help explain biological differences in addiction risk between men and women.

The takeaway

This research provides important insights into the biological mechanisms driving cocaine addiction, moving beyond the view of addiction as simply a personal failure. By understanding the role of proteins like DeltaFosB in altering brain circuits, scientists can work towards developing new pharmaceutical therapies to help the over 1 million Americans struggling with this devastating disease.