Potential Drug Target For Treating Cocaine Abuse Found

In an article published in the February 23, 2005, issue of The Journal of Neuroscience, Jonathan Katz and his colleagues at the National Institute on Drug Abuse (NIDA) report the results of experiments showing that mice treated with a substance similar to the drug benztropine did not show any of the typical hyperactive behavior when later injected with cocaine. This effect wore off after a day.

Cocaine produces intense feelings of euphoria by increasing the amount of dopamine that is sent from one neuron to another within the brain reward system. Dopamine signals pleasure and reward by binding to receptors on the receiving neurons, after which it is reabsorbed for later use by a protein that transports it back into the sending neuron. But cocaine blocks the mechanism that transports dopamine, causing it to build up and send an unceasing message of pleasure – the cocaine high.

Researchers have long searched for "a molecule that would block cocaine's effects on the transporter without inhibiting the transporter by itself," notes Eric Nestler, chair of psychiatry at the University of Texas Southwestern Medical Center in Dallas.

"This article reports early studies with just such a compound." Although the results are preliminary, this breakthrough shows that it may be possible to develop drugs that block cocaine's stimulating effects, and perhaps its power to addict, Nestler says.

Researchers previously thought that different chemicals that prevent the reabsorption of dopamine would all have the same stimulating effect on the brain. The new study shows this may not be true. "In fact, the interaction between dopamine trans-porters and the substances that bind to them may depend on the chemical structure of those substances," says NIDA's Amy Newman, who synthesized the compound. The researchers found that their novel drug made contact with transporters slowly – about 10 times slower than cocaine – which, they speculate, may be why it does not have a stimulating effect.

Between 2 million and 3.2 million people in the United States – about 1 percent of the population - use cocaine, according to estimates. Of this number, more than 550,000 are crack users. In 2002, 1.5 million Americans were thought to be dependent on or abusing cocaine. "Cocaine is capable of destroying not only the lives of those addicted, but also the lives of those around them," says Katz. "An effective treatment for cocaine addiction would be of immeasurable help to these individuals and their families."

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The Journal of Neuroscience is owned and published by the Society for Neuroscience, an organization of more than 36,000 basic scientists and clinicians who study the brain and nervous system. Katz's colleagues include Amy Newman, Rajeev Desai, Theresa Kopajtic, and Mikhail Koffarnus. Katz can be reached via the NIDA press office at 301-443-6245.