A recent study published has identified a brain protein that may help explain why cocaine addiction is difficult to overcome.
Researchers at Michigan State University found that repeated cocaine usage changes communication between memory and reward circuits in the brain, increasing the drive to seek the drug even after the person stops using it.
The protein, called DeltaFosB, builds up in the brain’s reward and memory circuits with repeated cocaine exposure.
Researchers found that the protein acts as a genetic switch, altering how neurons behave and intensifying the drive to seek the drug.
“Addiction is a disease in the same sense as cancer,” A.J. Robison, associate professor of neuroscience and physiology and the study’s senior author, said. “We need to find better treatments and help people who are addicted in the same sense that we need to find cures for cancer.”
Cocaine addiction affects at least one million Americans, but no FDA-approved medication exists to treat it. Unlike opioids, cocaine withdrawal does not produce severe physical symptoms, but quitting remains deeply difficult. Roughly 24% of users return to weekly cocaine usage within a year and another 18% re-enroll in treatment.
Lead author Andrew Eagle used a specialized form of CRISPR gene-editing technology to study DeltaFosB in mouse models. The protein was found to regulate the circuit connecting the brain’s reward center. The nucleus accumbens with the hippocampus, the region responsible for memory and learning.
“This protein isn’t just associated with these changes, it is necessary for them,” Eagle said. “Without it, cocaine does not produce the same changes in brain activity or the same strong drive to seek out the drug.”
The team identified a second gene called calreticulin which is regulated by DeltaFosB after long-term cocaine exposure. Calreticulin was found to accelerate the brain pathways that reinforce drug-seeking behavior by altering how neurons communicate with each other.
Robison’s team is partnering with researchers at the University of Texas Medical Branch in Galveston to develop compounds that target DeltaFosB directly. The project, funded by the National Institute on Drug Abuse, aims to create molecules that control how the protein binds to DNA.
“If we could find the right kind of compound that works in the right way, that could potentially be a treatment for cocaine addiction,” Robison said. “That’s years away, but that’s the long-term goal.”
Although the research was conducted in mice, scientists say many of the implicated genes and neural circuits are shared across species, lending weight to the possibility that findings will translate to humans.
Future research will explore how sex hormones influence these brain circuits and whether cocaine affects male and female brains differently, a distinction researchers believe could inform more personalized addiction treatments down the line.
