Howard Gillman Chancellor | University Of California, Irvine
Howard Gillman Chancellor | University Of California, Irvine
A team of researchers led by the University of California, Irvine has discovered that an antioxidant found in rosemary extract can reduce volitional intakes of cocaine by moderating the brain’s reward response. This finding offers a new therapeutic target for treating addiction.
The study, recently published online in the journal Neuron, describes the team's focus on a region of the brain called the globus pallidus externus (GPe), which regulates reactions to cocaine. Researchers found that within the GPe, parvalbumin-positive neurons are crucial in controlling responses to cocaine by altering the activity of neurons releasing dopamine.
“There are currently no effective therapeutics for dependence on psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” said Kevin Beier, UC Irvine associate professor of physiology and biophysics. “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 globus pallidus externus parvalbumin-positive cells become more excitable after exposure to cocaine. This caused a drop in the expression of certain proteins that encode membrane channels usually helping keep globus pallidus cell activity in check. Researchers discovered that carnosic acid, an isolate of rosemary extract, selectively binds to these affected channels, reducing response to the drug.
“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 the most vulnerable,” Beier said. “Furthermore, it’s possible that carnosic acid could be given to those at high risk to reduce the response to cocaine.”
Future research will include assessing negative side effects of carnosic acid and determining ideal dosage and timing. The team is also interested in testing its efficacy in reducing desire for other drugs and developing more potent variants.
In addition to UC Irvine researchers, scientists from the University of West Virginia and the University of Colorado participated in this study.
This work was supported by grants from various organizations including the National Institutes of Health and One Mind.
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