UC Irvine Study Offers Insight into Potential Interventions for Cocaine Use Disorder

Researchers from the UC Irvine School of Medicine have identified a protein involved in regulating cocaine intake. The findings suggest that blocking this protein could help address substance use disorders.

Although there is currently no medication for treating cocaine use disorder, we are now one step closer to understanding how cocaine manipulates circuits in the brain to reinforce drug-seeking behavior.

In a new study, UC Irvine researchers have identified a protein involved in regulating cocaine intake. The findings, published in an article in Nature Communications, suggest that blocking the activity of this protein could help address substance use disorders.

“Cocaine alters neuronal circuits by increasing dopamine release in areas of the brain that elicit reward, which leads to substance use disorders in humans,” explains Lauren Otsuka, a PhD candidate in the UC Irvine School of Medicine who helped lead the study. “Use of genetically modified mice lacking the dopamine D2 receptor on cholinergic interneurons allowed us to identify an acetyltransferase involved in the epigenetic regulation of gene expression and discover its role in regulating cocaine intake.”

Blocking the activity of this protein could reduce cocaine use.

“We indeed found that an inhibitor of the acetyltransferase identified in this study eliminates the epigenetic changes of gene expression that lead to overexpression of proteins affecting the reward circuitries of the brain, which control cocaine intake in mice,” says Emiliana Borrelli, PhD, a professor of microbiology and molecular genetics who advises Otsuka. “Our findings could pave the way for the development of pharmacological interventions that target the protein that we identified.”

The next step for the researchers is to delineate which genes downstream of the acetyltransferase participate in escalating drug intake.

This work was funded in part through grants from the National Institutes of Health (NIH).