Researchers studying the impact of cocaine in mice have found that just one exposure to the drug can create changes in brain cells that persist for at least two weeks. Their findings are being presented today (Tuesday) at the Federation of European Neuroscience Societies (FENS) Forum 2026.
Cocaine is a high addictive drug that can cause anxiety and paranoia in users, and can lead to heart damage, impotence and poor mental health in the long term. According to the UN Office on Drugs and Crime, cocaine use is at an all-time high, with an estimated 25 million users worldwide.
The research was presented by Ana Pombo, Bloomberg Distinguished Professor at Johns Hopkins University, Baltimore, US, and Guest Group Leader at the Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
We know that cocaine hijacks the reward machinery of the brain. Most people do not become addicted after using cocaine once, but many do after a second use or repeated exposures. However, we don't know enough about what is happening to brain cells exposed to cocaine and whether these effects are long-lasting.
We have been using mice to see where the brain stores the memory of taking cocaine for the first time and to understand why addiction occurs after repeated use, even when cocaine use is months or years apart."
Ana Pombo, Bloomberg Distinguished Professor, Johns Hopkins University, Baltimore, US
Professor Pombo and her colleagues used a technique called genome architecture mapping to understand the effects of cocaine on mouse brains. This approach makes it possible to study how genetic material is organized inside a cell. Although genes provide a blueprint for all cells in the body, their three-dimensional organisation can dictate when genes are switched on or off in any individual cell.
Compared to mice not exposed to cocaine, researchers found that the three-dimensional structure of the genome was extensively altered in brain cells called dopaminergic neurons in the ventral tegmental region of the midbrain. This part of the brain is known to play an important role in reward and motivation. The changes could be seen 24 hours after exposure to cocaine, but they persisted and some were even greater two weeks after exposure.
For example, amongst these changes, they found that a single cocaine exposure prompts the development of around 1,700 new 'chromatin domain insulation areas' – parts of the genome that can help regulate the activity of genes – and the loss of around another 1,100 of these areas.
The researchers also looked in detail at which genes were active and which were inactive in mouse brain cells exposed to cocaine compared with brain cells not exposed to cocaine.
This showed that exposed cells were producing more of some of the brain's signalling molecules, called neuropeptides, that have been linked to addiction in humans. Other genes that help the brain cell function normally had become less active.
Professor Pombo explained: "Our results suggest that a single exposure to cocaine 'rewires' the genome of these important brain cells. The fact that we found such big changes that persist for two weeks is unexpected and it suggests that the drug is leaving a longer-term 'scar' in the genome of the brain cells.
"These persistent changes may be setting the stage for a stronger response after a second dose of cocaine, which could help explain why the brain becomes susceptible to cocaine addiction. We still need to investigate how long these changes last for. Are they permanent, or can the brain cells recover over time? We also need to investigate how these changes translate to the risk of addiction."
Professor Christina Dalla from the National and Kapodistrian University of Athens, Greece, is chair of the FENS Forum communication committee and was not involved in the research. she said: "Cocaine use is a serious and growing problem around the world. We need to understand the effects of this drug and how people become addicted, but it's almost impossible to study these mechanisms in detail in the human brain, so instead we look at mice.
"In this study, scientists have identified profound and lasting changes in mouse brain cells after just one exposure to cocaine. This shows that cocaine can alter the structure of the genome in these cells and this alteration may persist over time. These findings challenge the idea that occasional recreational use of cocaine may be harmless as they suggest that one use could change our brains and raise the risk of addiction in the future.
"Researching these changes in greater detail could help us understand why some people are more likely than others to become addicted. This could also help us to find new ways to treat addiction."
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