to the neuron through the cell membrane and disrupt dopamine vesicles.
However, without transporters, dopamine cannot get out of the cell into
"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
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
Contact: Karyn Hede George
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