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Genetically altered mice no longer like cocaine

COLUMBUS , Ohio Researchers found that they could eliminate the rewarding effect of cocaine on mice by genetically manipulating a key target of the drug in the animal's brain.

While the researchers aren't suggesting that these genetic modifications be made in humans, the work brings to light the key protein that controls cocaine's effects in the body, which may help scientists develop medications that achieve the same results and therefore help addicts overcome their dependence.

Right now there are no such treatments on the market, said Howard Gu, the study's lead author and an associate professor of pharmacology and psychiatry at Ohio State University .

The study confirms that the dopamine transporter a protein that moves the neurotransmitter dopamine from outside of a neuron into the inside of the cell is a prime target for developing drugs to fight cocaine addiction.

"Cocaine blocks dopamine transporters, and this action ultimately is what makes a person feel high," Gu said. "We found that cocaine would not produce a high if it could not block the transporters."

He and his colleagues reported their findings the week of May 29 in the Proceedings of the National Academy of Sciences.

Dopamine is a chemical messenger vital to the regular functioning of the central nervous system. Under normal circumstances it flows into and out of neurons.

But cocaine blocks dopamine transporters from taking up dopamine, leaving it outside the cells, which excites the nervous system to the point where a cocaine user feels a high, Gu said.

He and his colleagues raised laboratory mice with genetic alterations in the gene that codes for the dopamine transporter.

"By doing so we created a dopamine transporter that resists cocaine but also retains its function of taking up dopamine and carrying it back to the neurons," Gu said.

The researchers tested cocaine's effects on normal mice and on mice with modifie
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Contact: Howard Gu
Gu.37@osu.edu
614-292-1324
Ohio State University
31-May-2006


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