A team of researchers led by the University of California, Irvine, has discovered that an antioxidant found in rosemary extract can reduce voluntary cocaine intake by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.
The study, recently published online in the journal Neurondescribes the team members’ focus on a region of the brain called the external globus pallidus, which acts as a gatekeeper regulating how we react to cocaine. They found that within the external globus pallidus, parvalbumin-positive neurons are crucial for controlling the response to cocaine by changing the activity of neurons that release the pleasure molecule dopamine.
“There are currently no effective treatments for dependence on psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” said corresponding author Kevin Beier, associate professor of physiology and biophysics at UC Irvine. “Our study deepens our understanding of the basic brain mechanisms that increase vulnerability to substance use disorder-related outcomes and provides a foundation for the development of new interventions.”
Findings in mice revealed that parvalbumin-positive cells in the external globus pallidus, which indirectly influence dopamine release, became more excitable after being exposed to cocaine. This caused a drop in the expression of certain proteins encoding membrane channels that usually help keep globus pallidus cell activity in check. The researchers found that carnosic acid, an isolate from rosemary extract, selectively bound to the affected channels, providing a pathway to reduce drug response in a relatively targeted manner.
“Only a subset of individuals are vulnerable to developing a substance use disorder, but we cannot yet identify who they 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. “Furthermore, it is possible that carnosic acid could be given to high-risk individuals to reduce response to cocaine.”
The next steps in this research include further evaluating the negative side effects of carnosic acid and determining the ideal dosage and timing of its administration. The team is also interested in testing its effectiveness in reducing the desire for other drugs and developing more potent and targeted variants.
In addition to the UC Irvine researchers, scientists from West Virginia University and the University of Colorado participated in the study.
This work was supported by grants from the National Institutes of Health, One Mind, the Alzheimer’s Association, New Vision Research, the BrightFocus Foundation, and the Brain & Behavior Research Foundation.