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

said Jaber, a post-doctoral fellow.

Indeed, research with the knockout mouse shows that conserving existing dopamine may be more effective.

"When we measured the amount of dopamine being released in the knockout mice, we were astounded to find they make only 5 percent to 10 percent the normal amount of dopamine, about the same as Parkinson's patients," said Caron. "Yet we thought the dopamine levels would be much higher than normal because without the transporter protein, there would be no way to remove excess dopamine from the synapse."

To resolve this apparent paradox, Jones and Wightman measured how long dopamine stays in the synapse after it is released. Their measurements showed that in a normal mouse, the dopamine is scavenged by the transporter protein in less than one second. However, in the knockout mice with no dopamine transporter protein, the dopamine stays in the synapse at least 100 times longer. Because dopamine is staying in the synapse longer, it prolongs the neurotransmission like cocaine or amphetamine would, even though there is very little of it.

The researchers realized this very dopamine-conservation strategy could be used to treat Parkinson's patients. Because Parkinson's patients make very little dopamine, the trick is to keep what little dopamine they have in the synapse longer, significantly increasing neurotransmission, Caron said. This could be achieved with drugs that selectively block the transporter protein. Such a strategy may prove to be more potent than standard treatments. Giving more dopamine to Parkinson's patients, as is done now, just keeps the active transporters busy longer, he said.

"Blocking the transporter with therapeutic drugs should greatly benefit Parkinson's patients," Caron said. "We believe these findings could have profound implications for the treatment of Parkinson's disease."

Knockout mice and schizophrenia

The researchers believe the mice may acc
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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University
29-Apr-1996


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