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Potential drug target for treating cocaine abuse found

WASHINGTON, DC February 17, 2005 -- A substance similar to a drug used in the treatment of Parkinson's disease blocks the stimulating effects of cocaine and could potentially be used to develop drug therapy for cocaine abuse, new research shows.

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 chemi
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Contact: Elissa Petruzzi
elissa@sfn.org
202-462-6688
Society for Neuroscience
22-Feb-2005


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