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Gene-Altered Mouse May Provide New Insights To Parkinson's Disease, Substance Abuse And Schizophrenia

nts to neutrotransmitter transporters as the most important determinant of the strength and duration of cellular communications in the nervous system."

Dr. Ralph Snyderman, chancellor for health affairs at Duke, said, "These findings represent a superb example of the way in which basic research in academic medical centers leads to practical benefit. This discovery may well change our understanding of the nature of addiction and lead to new treatments for psychiatric disorders and Parkinson's disease. It once again shows how our nation's commitment to research is needed to provide practical solutions for common health care problems."

Insights into the mechanism of amphetamine drugs derived from studying the "knockout" mice should yield new strategies for treating amphetamine addiction, Caron said.

"Much of what we know about dopamine's function comes from studies of drugs that tamper with the dopamine system," he said. Cocaine, for example, temporarily blocks the transporter from outside the cell, so the dopamine remains at high concentrations in the synapse and continues to stimulate adjacent neurons, producing cocaine's characteristic "high."

Amphetamines, by contrast, are believed to enter the neuron via both the transporter and directly through the cell membrane, where they burst dopamine vesicles inside the cell and promote the release of dopamine.

"What happens when amphetamines break dopamine vesicles has been a matter of some speculation, since it has never been directly tested,"said Jones, a post-doctoral fellow.

These studies provide the first direct demonstration that the dopamine transporter is absolutely required for amphetamine's releasing action on dopamine. Amphetamine appears to reverse the dopamine transporter pump so instead of pumping dopamine into the cell, it pumps dopamine out of the cell, Caron said.

In the knockout mice with no dopamine transporters, amphetamines can still get in
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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University
29-Apr-1996


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