Researchers have found that a single exposure to cocaine can create changes in mouse brain cells that persist for at least two weeks, according to findings presented on July 6 at the Federation of European Neuroscience Societies Forum 2026.
The research was presented by Ana Pombo, Bloomberg Distinguished Professor at Johns Hopkins University and Guest Group Leader at the Max Delbrück Centre for Molecular Medicine. Pombo said, "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."
Pombo and her colleagues used genome architecture mapping to study how genetic material is organized inside mouse brain cells following cocaine exposure. They discovered extensive alterations in the three-dimensional structure of the genome within dopaminergic neurons located in the ventral tegmental region of the midbrain—a region important for reward and motivation. The researchers observed these changes as early as 24 hours after exposure, with some persisting or even increasing two weeks later.
Among their findings were approximately 1,700 new chromatin domain insulation areas developing and around 1,100 such areas being lost following a single dose of cocaine. Further analysis revealed that exposed cells produced more neuropeptides linked to addiction in humans, while other genes necessary for normal cell function became less active.
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." She added: "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 also need to investigate how these changes translate to the risk of addiction."
Commenting on this research, Professor Christina Dalla from National and Kapodistrian University of Athens said, "In this study, scientists have identified profound and lasting changes in mouse brain cells after just one exposure to cocaine... 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 future." Dalla also noted further research could help identify why some individuals are more likely than others to become addicted.
