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University scientists discover role for serotonin in ADHD

Thanks to a new set of Duke-based research, medical science may be a step closer to understanding attention deficit hyperactivity disorder.

The research, published in today's issue of Science, one of the most prominent scientific journals, suggests that ADHD might be caused by an imbalance of the neurotransmitter serotonin rather than dopamine, which is the more commonly suspected culprit.

Little is known about ADHD, which affects thousands of children in this country. Between 3 percent and 6 percent of children between ages 4 and 14 are thought to have the condition.Children with ADHD have difficulty paying attention to directions and often have trouble learning. In some cases, affected children experience problems controlling what they say or do, sometimes hitting other children.

When doctors diagnose ADHD, treatment often includes psychiatric treatment as well as drug therapy. But doctors and parents are increasingly turning to the popular psychostimulant Ritalin to calm their children. No one is quite sure how Ritalin works, although before the recent study it was believed to have acted on the dopamine system. Patients with ADHD "behave as if they have a dopamine imbalance" said Caron, although he stressed that the exact chemical cause of ADHD is not known.

But study authors Marc Caron, professor of cell biology and Howard Hughes Medical Institute investigator, and Raul Gainetdinov, a research associate, concluded that Ritalin acts on the receptor of the neurotransmitter serotonin rather than on a receptor of the neurotransmitter dopamine.

In the experiment, Caron and his team used "knockout" mice to isolate the dopamine system. "Knockout" mice are mice that have been genetically engineered to lack a certain trait, which is thus "knocked out." These "knockout" mice were created with no dopamine receptors, which are molecules that "clean up" leftover dopamine. This made the dopamine in their brains reach five times a normal level.

Both normal and "knockout" mice were given Ritalin The amount of dopamine in their brains was then measured after 20 minutes. Results showed that normal mice had increased levels of dopamine while the "knockout" mice had no such change.

"This finding indicated that Ritalin couldn't be working on dopamine," Gainetdinov said in a press release.

The researchers then gave the "knockout" mice a drug that blocks the reuptake of serotonin-known by the market name Prozac. Consequently, serotonin levels increased in the mice's' brains, which in turn reduced their hyperactivity.

The findings can help scientists "design drugs that are more selective and safer than existing drugs" Caron said. One of the drawbacks to Ritalin is its side effects such as insomnia, nausea and, less commonly, anorexia.

Caron went on to say that further research is needed to determine which serotonin receptor Ritalin affects.

"We know serotonin is mediated by 15 receptors. We need to find the one that psychostimulants affect," Caron said.

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