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Genes may be central to cocaine addiction

Two related genes that help control signaling between brain cells may be central components of the biological machinery that causes cocaine addiction, researchers have found. Peter Kalivas and his colleagues found that deleting either of two genes in the Homer family in mice produced the same symptoms seen in withdrawal from cocaine. The researchers said that their findings could open a new research pathway to understanding how genetic susceptibility to addiction interacts with environmental factors to cause addiction.

Studies by other researchers had suggested that the proteins produced by the Homer genes might play a role in cocaine addiction. Members of the family were known to be activated by cocaine, and reduction of activity in the genes had been linked to cocaine withdrawal.

So, to unequivocally test the involvement of the Homer genes in cocaine addiction, Kalivas and his colleagues individually knocked out the genes in mutant mice and tested the behavioral and biological effects. In one behavioral test, they placed the knockout mice in one of two linked chambers after cocaine administration. One was a "comfortable" darkened chamber with nesting material, and the other was an "uncomfortable" bare, white, brightly lit chamber. The researchers found that the mice lacking Homer1 or Homer2 genes showed greater preference for the chamber that they associated with receiving cocaine, compared to normal controls. The knockout mice also showed hyperactivity characteristic of withdrawal.

The Homer2 knockout animals also showed a greater motivation to self-administer cocaine by pressing a lever than did normal mice. Also, the knockout animals showed neurochemical changes associated with cocaine addiction, including reduced base levels of the neurotransmitter glutamate in the region of the brain known to be involved in addiction. They also showed increased levels when receiving cocaine. Such brain chemical changes are characteristic of addiction,
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
4-Aug-2004


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