Neuroscientists are known for doing some strange things to mice in their pursuit of learning about the brain. One such strange thing is training mice to self-administer cocaine, but it’s all for a good cause: Self-administration can help us understand the biological underpinnings of substance use disorders.
In a study recently published in Neuron, researchers found that cocaine use changes the DNA in mouse brains, specifically in the brain regions associated with reward. After consuming cocaine, the DNA in their brain cells had different chemical modifications known as epigenetic changes. These epigenetic changes also altered the types of RNAs the cells made through splicing. In this process, pieces of genes are left out or added in to create different RNAs that create different proteins.
Scientists have known RNA splicing is particularly important for neurons, and the researchers behind this mouse study saw many epigenetic and splicing changes after the mice consumed cocaine. Then, they artificially recreated one specific epigenetic change at a gene called Srsf11. This led Srsf11 to be spliced differently. However, Srsf11 is also a gene that controls splicing across the genome, meaning that changes to it had ripple effects in the mice. This one change also altered splicing across a few hundred other genes, some of which were previously implicated in substance use disorders. Most interestingly, the mice with the modified version of Srsf11 self-administered more cocaine, showing that these sorts of changes in the brain may underlie addiction.
Some researchers argue that increasing the body of evidence for the biological basis of substance use disorders reduces stigma against people who use substances, though the effectiveness of this in public messaging is debated. Regardless, though we continue to see evidence that substance use disorders are biologically-driven, there are currently no approved drugs to treat the overuse of cocaine. Epigenetics and RNA splicing may be promising targets for future medical interventions.