Emory Report

September 11, 2000

 Volume 53, No. 3

Yerkes' Kuhar looking for help for cocaine addicts

By Poul Olson

Michael Kuhar and a team of neuroscientists at Yerkes 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 multiyear grant from the National Institute on Drug Abuse, the study was reported in the August issue of The Journal of Pharmacology and Experi-mental Therapeutics.

Using rat models, Kuhar and his team injected the 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 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."

Cocaine and methamphetamine are the only illicit drugs for which there exists no therapeutic substitute to control craving. An estimated 2 million Americans use cocaine and methamphetamine.

Given the observed behavioral changes, Kuhar believes the CART peptide could somehow influence the psychostimulant effects of cocaine and methamphetamine. Its ability to spur conditioned place preference further suggests a role 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 peptide's role 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 Heather Kimmel and Wenhe Gong, Stephanie Dall Vechia and Richard 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. His colleague at Yerkes, Leonard Howell, is currently testing the compounds as part of a five-year effort by the National Institute on Drug Abuse (NIDA) and the Office of National Drug Control Policy to develop a medication for treating cocaine addiction.

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