Scientists have discovered a new clue to how addiction works in the brain and why it can be so hard for people with substance use disorders (SUDs) to avoid relapse.
The study, published in Biological Psychiatry, focuses on a brain enzyme called HDAC5 and a gene it controls, Scn4b. These molecules may play a key role in how the brain forms strong memories related to drug use—memories that can later trigger cravings and relapse.
Substance use disorder is a serious and long-lasting condition that affects many people around the world. In the United States, drug-related deaths remain at record levels, and stimulant use continues to rise. Even though many programs aim to help people quit, relapse is still very common.
That’s partly because the brain tends to form powerful associations between the feelings of reward from drugs and the environment in which they were used. These “drug memories” can linger for years and resurface easily, even after long periods of not using the drug.
The new research helps explain how these memories are formed and held so strongly in the brain. The scientists found that HDAC5, an enzyme that controls how genes are turned on or off, plays an important role in limiting the activity of the Scn4b gene.
This gene helps control how excitable certain brain cells are—specifically, neurons in the nucleus accumbens, a part of the brain linked to reward and addiction.
When HDAC5 is not doing its job properly, Scn4b is more active, which increases the excitability of these neurons. This, in turn, makes it easier for the brain to form strong and long-lasting links between drug use and the places or situations where the drug was taken. These strong associations can later act as “triggers,” increasing the chance of relapse.
The research team used many advanced techniques, such as brain scans, genetic analysis, computer modeling, and behavioral studies in rats. One of the most surprising findings was that the Scn4b gene influenced cocaine-seeking behavior but did not affect seeking for a natural reward, like sugar.
This means that the gene may be involved in drug-specific brain changes that don’t impact other kinds of reward-seeking.
This discovery is important because it highlights a new possible target for future treatments. Right now, there are no approved medications that specifically treat cocaine addiction. But by focusing on the HDAC5 enzyme or the Scn4b gene, scientists may be able to develop therapies that weaken drug-related memories without affecting other brain functions.
Dr. John Krystal, editor of the journal, said this study supports the idea that addiction changes gene activity in the brain in lasting ways, helping explain why relapse is so common.
Dr. Christopher Cowan, one of the lead researchers, added that their results show HDAC5 helps keep certain brain cells from becoming too excitable, which may prevent those strong drug memories from forming in the first place.
Another lead researcher, Daniel Wood, said that discovering how SCN4B is involved only in drug-related behavior—not natural rewards like food—is exciting and unexpected. It could lead to new treatments that specifically reduce the risk of relapse without affecting everyday motivation or pleasure.
In summary, this study reveals that addiction may be partly driven by changes in gene expression that make the brain more likely to form powerful drug-related memories. The HDAC5 enzyme and Scn4b gene could be key players in this process.
Targeting these could offer a new way to help people stay in recovery and avoid relapse, especially for conditions like cocaine addiction where treatment options are currently limited.
If you care about wellness, please read studies about how ultra-processed foods and red meat influence your longevity, and why seafood may boost healthy aging.
For more health information, please see recent studies that olive oil may help you live longer, and vitamin D could help lower the risk of autoimmune diseases.
The research findings can be found in Biological Psychiatry.
Copyright © 2025 Knowridge Science Report. All rights reserved.
