July 19, 2000 ATLANTA July 19, 2000 -- Dr. Michael Kuhar and a team of neuroscientists at the Yerkes Regional Primate Research Center of Emory University have found that a naturally occurring neurotransmitter produces behaviors associated with cocaine and methamphetamine. The finding suggests a role for the brain chemical, called CART (Cocaine- and Amphetamine-Regulated Transcript) peptide, in modulating or mediating the actions of drugs and a perhaps potential new avenue for treating addiction. Funded by a multi-year grant from the National Institute on Drug Abuse, the study will be reported in the August issue (vol. 294, no. 2) of The Journal of Pharmacology and Experimental Therapeutics.
Using rat models, Kuhar and his team injected CART peptide directly into the ventral tegamental area (VTA), a region of the brain stem involved in addiction and feelings of euphoria. The VTA is also one of several areas where the neurotransmitter occurs naturally. In their experiments, the researchers observed increased locomotor activity, comparable to that seen with cocaine administration.
In a separate experiment, Kuhar's team found that the administration of CART peptide caused the rats to return repeatedly to the place where they received the initial injection. The behavior, known as conditioned place preference, has been observed during animal studies on the effects of cocaine on the brain. "CART peptide seems to act as an endogenous cocaine," said Kuhar. "The rats perceived the neurotransmitter as a good feeling and wanted to reinforce that 'euphoria' by returning to the place where they received it."
Given the observed behavioral changes, Kuhar believes CART peptide could somehow influence the psychostimulant effects of cocaine and methamphetamine. Its ability to spur conditioned place preference further suggests a role for the neurotransmitter in the drug addiction process.
Previous studies have identified CART peptide in areas of the brain directly affected by cocaine and methamphetamine. Scientists have also measured increased levels of CART when cocaine was administered.
"This latest discovery about CART's cocaine-like properties gives us a potential therapeutic target for medications designed to treat addiction," said Kuhar. "Theoretically, it might be possible to modulate the neurotransmitter in such a way that craving for cocaine or methamphetamine might be altered."
The next steps will be to ascertain the role of CART peptide in other areas of the brain and possibly extend the studies to primates. As a consequence of animal studies on the effects of cocaine on the brain, scientists have determined that CART peptide also influences hunger, stress, endocrine control, and sensory processing.
In addition to Kuhar, the study's authors include Drs. Heather Kimmel and Wenhe Gong, Stephanie Dall Vechia, and Richard G. Hunter.
A nationally-known expert on the biological underpinnings of drug addiction, Kuhar has also been instrumental in the development of a new class of cocaine analogues called phenyltropanes. Kuhar's colleague at Yerkes, Dr. Leonard Howell, is currently testing the compounds as part of a five-year effort by NIDA and the Office of National Drug Control Policy to develop a medication for treating cocaine addiction.
Cocaine and methamphetamine are the only illicit drugs for which there exists no therapeutic substitute to control craving. An estimated two million Americans use cocaine and methamphetamine.
The Yerkes Regional Primate Research Center is part of the Woodruff Health Sciences Center of Emory University. It is the oldest scientific institution dedicated to primate research. Yerkes' programs cover a wide range of biomedical and behavioral sciences.
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