Yerkes researchers discover natural brain chemical reduces effects of cocaine

Researchers led by Jason Jaworski, PhD, and Michael Kuhar, PhD, both at the Yerkes National Primate Research Center at Emory University, have shown that CART peptide, a chemical that occurs naturally in both the rodent and human brain, reduces some effects of cocaine when additional amounts are administered to the region of the brain that is associated with reward and addiction. These findings, which were presented on November 8 at the Society for Neuroscience meeting in New Orleans, appear in the December issue of the Journal of Pharmacology and Experimental Therapeutics and suggest CART peptide receptors in the brain could be targets for developing medications to treat cocaine abuse.

For their study, Dr. Jaworski, a post-doctoral fellow, and Dr. Kuhar, chief of the Neuroscience Division at Yerkes and a Georgia Research Alliance Eminent Scholar, infused CART peptide into the nucleus accumbens (NA) of rodents to determine how it affects the increase of body movement, or locomotor activity, that is widely seen as one effect of psychostimulant drugs. The researchers observed that the cocaine-induced movement was reduced after the rodents received CART peptide. “This is the first study to demonstrate CART peptides in the nucleus accumbens hinder the effects of cocaine,” said Dr. Jaworski. “Our findings open a door to develop potential treatment options for cocaine addiction.”

When infused into other areas of the “pleasure pathway,” the part of the brain in both rodents and humans that is activated when cocaine is administered, CART peptide has been shown to produce minimal psychostimulant-like effects. “Past studies have shown CART peptide is slightly cocaine-like in other areas of the brain, but nevertheless inhibits further stimulation from the drug,” said Dr. Kuhar. “While additional research will be necessary, we have demonstrated the importance of CART peptide in combating or slowing down some of the effects of cocaine.”

The researchers’ immediate next steps are to study CART peptide’s mechanism of action on the brain, as well as to determine if rodents who have been treated with CART peptide will administer less cocaine to themselves than those that have not been treated. They hope to determine how CART peptide produces the “anti-cocaine” effect so they can one day begin to develop treatments for cocaine addiction in humans.

The Yerkes National Primate Research Center of Emory University is one of eight National Primate Research Centers funded by the National Institutes of Health. The Yerkes Research Center is a multidisciplinary research institute recognized as a leader in biomedical and behavioral studies with nonhuman primates. Yerkes scientists are on the forefront of developing vaccines for AIDS and malaria, and treatments for cocaine addiction and Parkinson’s disease. Other research programs include cognitive development and decline, childhood visual defects, organ transplantation, the behavioral effects of hormone replacement therapy and social behaviors of primates. Leading researchers located worldwide seek to collaborate with Yerkes scientists.