Researchers have discovered that an antioxidant in rosemary extract can reduce cocaine intake by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.

The study in the journal Nerve cell describes researchers’ focus on an area of ​​the brain called the globus pallidus externus, which acts as a gatekeeper and regulates how we respond to cocaine.

They found that parvalbumin-positive neurons in the GPe play a crucial role in regulating the response to cocaine, by altering the activity of neurons that release the pleasure molecule dopamine.

“There are currently no effective therapies for dependence on psychostimulants such as cocaine, which together with opioids pose a significant health burden,” said corresponding author Kevin Beier, an associate professor of physiology and biophysics at the University of California, Irvine.

“Our research deepens our understanding of the fundamental brain mechanisms that increase vulnerability to substance abuse-related outcomes and provides a basis for the development of novel interventions.”

Findings in mice showed that parvalbumin-positive globus pallidus externus cells, which indirectly affect dopamine release, became more excitable after cocaine exposure. This caused a decrease in the expression of certain proteins encoding membrane channels that normally help keep globus pallidus cell activity in check. The researchers found that carnosic acid, an isolate from rosemary extract, selectively binds to the affected channels, providing a way to reduce the drug response in a relatively specific way.

“Only a subset of individuals are vulnerable to developing a substance use disorder, but we can’t yet identify who those are. If globus pallidus cell activity can effectively predict response to cocaine, it could be used to measure likely responses and thus serve as a biomarker for those most vulnerable,” Beier said. “In addition, it is possible that carnosic acid could be given to people at high risk to reduce response to cocaine.”

The next steps in this research include thoroughly assessing negative side effects of carnosic acid and determining the ideal dosage and timing. The team is also interested in testing its effectiveness in reducing the need for other medications and developing more potent and targeted variants.

Scientists from West Virginia University and the University of Colorado participated in the study.

This work was supported by the National Institutes of Health, One Mind, the Alzheimer’s Association, New Vision Research, BrightFocus Foundation, and the Brain & Behavior Research Foundation.

Source: UC Irvine