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

to the neuron through the cell membrane and disrupt dopamine vesicles. However, without transporters, dopamine cannot get out of the cell into the synapse.

"Our results show the transporter is absolutely essential for amphetamine dependent transport of free dopamine into the synaptic space, to the exclusion of any other mechanism," Caron said. "In essence, no functional transporter would mean no amphetamine high. This information should provide new understanding of the mechanism of amphetamine drugs and new strategies for treating amphetamine addiction."

Besides dopamine's direct role in producing a drug-induced high, said Caron, recent studies have shown that dopamine plays a central role in the brain's reward centers. These dopamine-activated pleasure centers are key to the addictive reinforcing pattern, even though addictive substances such as alcohol, nicotine, and cocaine may exert their influence on many different areas of the brain, Caron said.

Additional background: Insights into Parkinson's disease
The research with the knockout mice could also provide new insights into the management of Parkinson's disease, said Caron. The mouse research may point the way toward drugs that maintain the higher levels of dopamine in the brains of Parkinson's sufferers.

In Parkinson's disease, dopamine-producing neurons in the brain's motor control center, called the substantia nigra, slowly deteriorate and die. Thus, Parkinson's disease begins with small tremors and progresses to a total inability to initiate movement. Currently incurable, Parkinson's disease affects almost a million Americans and 50,000 new cases are diagnosed each year.

Drug therapies for Parkinson's disease have focused on replenishing the body's diminished supply of dopamine.

"Nobody has ever considered the dopamine transporter as a target, in part because its crucial role in maintaining dopamine levels had never been fully appreciated,"

Contact: Karyn Hede George
Duke University

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