Repeated Cocaine Use Alters The Expression Of Genes In The Brain

It's a slippery slope. DedMityay/Shutterstock 

Everyone knows that drug addiction is an astonishingly hard cycle to get out of, yet a lack of understanding regarding what causes people to carry on using harmful substances makes it extremely difficult to provide effective treatments. However, a new study in the Journal of Neuroscience may have just illuminated one of the black spots in our knowledge of how addiction works, by revealing the way in which chronic cocaine use changes the way that genes are expressed in the brain.

The hippocampus is often thought of as the brain’s memory center, and is believed to be strongly implicated in the formation of associations that promote addiction. For example, repeated drug users often learn to associate particular places with drug-taking, which is why they find it so difficult not to use when they are in that environment.

Previous work has shown that the gene FosB plays a central role in mobilizing the hippocampus to create certain memories, so a team of researchers decided to investigate how chronic cocaine use interferes with the functioning of this gene in order to create drug-related associations.

Lab mice were split into two groups, one of which received regular doses of cocaine while the other was given a saline solution. The cocaine-fed mice quickly showed signs of having learned to associate the drug with the environment in which they received it.

Genetic analysis revealed that the expression of FosB was indeed elevated in the hippocampus of all the mice in this group, compared to the mice that had been given saline. Known as epigenetic modification, this upregulation of a particular gene occurs when certain molecules become attached to the histone proteins around which DNA is arranged.

When the researchers then blocked these epigenetic modifications from occurring, the mice seemed to lose the ability to form associations between cocaine and their environment.

Based on these findings, the authors conclude that the epigenetic regulation of FosB in the hippocampus is “critical for cocaine-related learning,” and that the repeated use of the drug activates the gene in order to allow the hippocampus to form addictive memories.

The researchers hope that this work can help to guide the development of future treatments for cocaine addiction, and while much more work is needed on that front, this study does at least provide some new insight into why drug use is such a slippery slope.

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