Relapse to cocaine use is not simply a matter of weak willpower. New research shows that persistent biological changes in the brain may be to blame. Scientists have found that cocaine use changes the brain’s circuitry and can make it very difficult to resist the urge to return to the drug.
Researchers at Michigan State University have discovered that cocaine changes the function of the hippocampus. This area of the brain plays an important role in memory and learning. Their research was supported by the National Institutes of Health. scientific progressexplains why cocaine dependence is so difficult to treat and points to new drugs that may help.
“Addiction is a disease in the same sense as cancer,” said lead author AJ Robison, professor of neuroscience and physiology. “Just like we need to find a cure for cancer, we need to find better treatments to help addicts.”
Why it’s hard to quit cocaine
Cocaine addiction affects at least 1 million people across the United States, but there are currently no FDA-approved drugs specifically designed to treat cocaine addiction. Unlike opioids, stopping cocaine use usually does not cause severe physical withdrawal symptoms. Yet, it is still very difficult to quit.
The reason for this is the effect that cocaine has on the brain. This drug floods your reward center with dopamine, a chemical associated with pleasure and motivation. This surge creates powerful positive reinforcement, causing the brain to interpret cocaine use as beneficial rather than harmful.
Even if someone is able to stop using cocaine, relapse rates remain high. Approximately 24% of people return to weekly cocaine use, and an additional 18% re-enroll in treatment within a year.
Protein that drives cocaine craving
Andrew Eagle, the study’s lead author and a former postdoctoral fellow in Robison’s lab, identified a key factor behind this persistent motivation. This molecule is a protein called DeltaFosB.
To investigate its role, Eagle used a specialized form of CRISPR technology to study how DeltaFosB affects specific brain circuits when mice are exposed to cocaine.
Experiments using mouse models revealed that DeltaFosB functions like a genetic switch. It activates or suppresses genes in the circuit that connects the brain’s reward center with the hippocampus, which acts as the brain’s memory hub. Continued cocaine use causes proteins to build up in this circuit. As its levels increase, the behavior of neurons changes and the response of circuits to drugs changes.
“This protein is not only involved in these changes, but is necessary for them,” Eagle said. “Without it, cocaine wouldn’t cause the same changes in brain activity or the same strong urges to seek the drug.”
Genes that enhance the search for cocaine
The researchers also identified additional genes regulated by DeltaFosB after chronic cocaine exposure. One of these genes is calreticulin, which helps control how neurons communicate with each other.
Their experiments showed that calreticulin increases activity in brain pathways that encourage individuals to keep seeking cocaine, effectively accelerating brain processes that reinforce addiction.
Potential targets for future treatments
Although the study was conducted in mice, the results may also apply to humans, as many of the same genes and neural circuits are shared across species.
Robison’s team is currently working with researchers at the University of Texas Medical Branch in Galveston, Texas, to develop compounds that specifically target DeltaFosB. The project is supported by a grant from the National Institute on Drug Abuse and focuses on creating and testing molecules that can control how DeltaFosB binds to DNA.
“If we can find the right kind of compound that works in the right way, it could be a treatment for cocaine addiction,” Robison said. “That’s many years away, but that’s the long-term goal.”
Future research on gender differences in addiction
The next stage of research will investigate how hormones affect these brain circuits. The research team also plans to investigate whether cocaine affects the brains of men and women differently.
Understanding these differences may shed light on why the risk of addiction may differ for men and women and may guide more individualized treatment approaches.
