Research shows cocaine 'reward' picture more complicated than scientists thought

CHAPEL HILL -- University of North Carolina at Chapel Hill scientists working with colleagues at Duke University have discovered that even after dopamine and norepinephrine systems are disrupted in specially modified laboratory animals, cocaine still provides reinforcing "rewards" to animals that ingest it.

Their study, reported Saturday (April 12) at a meeting of the American Society for Pharmacology and Experimental Therapeutics in San Diego, shows the brain's ability to process the addictive drug is more complex than many researchers believed. It also brings medical science a bit closer to the day when effective therapies will be available to treat cocaine addiction, the scientists say.

Dr. Linda Dyksta, William Rand Kenan Jr. professor of psychology and pharmacology and dean of the graduate school at UNC, presented the team's findings. Other scientists involved in the work included Drs. Marc G. Caron, James B. Duke professor, and Raul Gainetdinov, assistant research professor, both in cell biology at Duke.

"What we call transporters normally take up biological chemicals known as neurotransmitters such as dopamine and return them to neurons to be reprocessed," Dykstra said. "When transporters are blocked, however, dopamine will remain in the synapses of nerve cells."

Using techniques pioneered by UNC's Dr. Oliver Smithies, Excellence professor of pathology and laboratory medicine, Caron created genetically altered mice that lacked two of the transporters, one for dopamine and the other for norepinephrine. Such designer animals, dubbed "knock-out mice," have proven invaluable for studying the activity of many genes both in health and sickness.

It was possible, the scientists thought, that without those two mediators of cocaine's effects, the brain could not to process the drug normally. Hence, no reinforcement of the drug-taking would occur.

"By deleting first the dopamine transporter gene and then both the dopamine

Contact: David Williamson
University of North Carolina at Chapel Hill

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