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Discovery of new dopamine action may yield alternative psychiatric drugs

Durham, N.C. Duke University Medical Center researchers have discovered a new mechanism by which chronically high levels of the neurotransmitter dopamine exert their effects on the brain. Normally associated with triggering feelings of pleasure, excess concentrations of dopamine underlie schizophrenia, attention deficit hyperactivity disorder and other psychiatric conditions. The findings therefore provide new research avenues to understand and potentially manage such dopamine-related human disorders, the researchers said.

"We've thought that neurotransmitters relay messages to the brain in two speeds: fast and slow," said lead author of the study Jean-Martin Beaulieu, Ph.D. of Duke. "However, our new findings reveal that brain receptors that respond to dopamine actually have two slow modes: one that takes place over a period of minutes and a second -- newly discovered -- that lasts for hours. In fact, it may be that this effect continues for as long as dopamine remains in the system."

This sustained action of dopamine may be particularly important for understanding psychiatric conditions, which are characterized by persistently high levels of the brain messenger, Beaulieu said. The researchers report their findings in the July 29, 2005, issue of Cell.

"This mechanism appears to be more important than those earlier described for prolonged stimulation by dopamine, as would be the case in those with psychiatric conditions," said senior author Marc Caron, Ph.D., of Duke. "The new pathway can now be evaluated for potential new inhibitors that might be better at controlling particular psychotic behaviors." Caron is a professor of cell biology at Duke and faculty member at the Duke Institute for Genome Sciences & Policy.

Dopamine's prolonged effects might also apply to understanding the impact of sustained drug use on the brain, Caron added. Virtually all addictive drugs, including cocaine and amphetamines, directly or indirectly raise dop
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
28-Jul-2005


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