News Release

Genetically modified mice provide information on treatments for cocaine dependence

Peer-Reviewed Publication

Federation of American Societies for Experimental Biology

Drug abuse places a tremendous burden on our nation each year, both in terms of crime, law enforcement demands, lost productivity, added costs of health care delivery, and premature death. Among those drugs that are abused, cocaine is considered one of the most powerful. Yet no effective medications exist to treat cocaine abuse, dependence or withdrawal.

In order to develop these needed medications, a better understanding of cocaine's brain mechanisms is required. Although it is known that cocaine acts on at least three different transporter systems -- the dopamine transporter, the serotonin transporter and the norepinephrine transporter -- it is not clear which combination of transporter systems holds the most potential as targets for developing treatments for cocaine abuse.

Recently, a collaborative research effort led by scientists at the University of North Carolina/Chapel Hill and Duke University used genetically-modified mice to provide information about the mediation of cocaine's rewarding effects. These findings promise to guide the development of potential medications for cocaine abuse. Drs. L.A. Dykstra, L.M. Bohn, R.M. Rodriguiz, W.C. Wetsel, R.R. Gainetdinov and M. G. Caron. University of North Carolina at Chapel Hill, Duke University, and Howard Hughes Medical Institute, presented their results at an American Society for Pharmacology & Experimental Therapeutics session at the Experimental Biology 2003 meeting in San Diego. In these studies, mice were genetically altered so they lacked two of the potential mediators of cocaine's effects. One of those mediators was the dopamine transporter, which is considered to be the primary site of cocaine's rewarding effects. The other mediator was the norepinephrine transporter.

Cocaine's rewarding effects were still apparent in mice that were lacking both the dopamine and the norepinephrine transporter. Indeed, cocaine was just as rewarding in mice lacking these targets as in control mice that had been raised under identical conditions, but did not have genetic deletions of both the dopamine and the norephinephrine transporter gene.

Since inactivation of dopamine and norepinephrine transporters in mice creates a situation that partially mimics cocaine's effects on dopamine and norepinephrine levels in the brain, these observations imply that cocaine has actions beyond these two targets. Researchers in this group have already suggested that the serotonin system may be an additional target for cocaine and these results are consistent with that contention. This research is supported by the National Institute of Drug Abuse.

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(American Society for Pharmacology and Experimental Therapeutics)


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