News Release

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

Peer-Reviewed Publication

University of North Carolina at Chapel Hill

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 and norepinephrine transporter genes and finding cocaine's reward effects still apparent, we concluded that a third transporter was involved," Dyksta said. "Our work and that of others suggests that would be the serotonin system, and there may be other systems we don’t know about yet."

Drug abuse damages the United States and its residents through crime, higher law-enforcement costs, productivity losses, heavier health-care costs, premature death and strains on families, she said. Cocaine is one of the most frequently abused drugs, but there are no effective medications for treating the abuse, dependence or withdrawal.

"We believe the laboratory work we’re doing with genetically altered mice is providing useful insights into how addiction works and how it one day can be prevented or cured," Dyksta said.

The National Institute of Drug Abuse supported the research.

Earlier this week UNC scientists, including Drs. Regina Carelli and Paul Phillips, also of psychology, and R. Mark Wightman of chemistry, drew international attention to their work by publishing a paper in the British journal Nature.

They used novel experimental techniques that allowed them to monitor dopamine levels in the brain in real time – 200 times faster than was possible before.

The researchers found dopamine levels significantly increased moments before laboratory rats decided to get more cocaine by pressing a bar that released the drug into their bloodstreams.

Their findings suggested that the chemical signal served as a promise of "reward" and specifically motivated the rodents to get more of the drug immediately in response to the craving.

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By David Williamson
UNC News Services


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