DURHAM, N.C. -- A study using genetically engineered mice suggests a different mechanism of action than scientists have hypothesized to explain how the drug Ritalin calms humans with attention deficit hyperactivity disorder (ADHD).
If confirmed in humans, the finding could lead to more effective drugs to treat a disorder that has long baffled and frustrated parents, physicians and doctors alike.
The study results are published in the Jan. 15 issue of the journal Science by Marc Caron, a Howard Hughes Medical Institute investigator at Duke University Medical Center, and Research Associate Dr. Raul Gainetdinov of the department of cell biology.
The researchers found evidence that Ritalin works by affecting levels of the brain chemical serotonin, which helps regulate mood and inhibit aggression and impulsive behavior. Current theory holds, however, that Ritalin calms people with ADHD by affecting the level of the brain chemical dopamine, whose actions include regulation of activity and locomotion. Both dopamine and serotonin are neurotransmitters, chemicals which are launched by neurons, or brain nerve cells, to trigger nerve impulse in neighboring neurons.
Caron and Gainetdinov made their discovery by genetically creating "knockout" mice lacking a protein called a dopamine transporter that scavenges the dopamine remaining in the spaces between neurons after the chemical has triggered a nerve impulse. Such transporters are a key part of the machinery for recycling neurotransmitters back into neurons for reuse.
Since the brains of the knockout mice had dopamine levels five times
normal, their neurons were firing at abnormally high rates, causing them to
behave as do humans with ADHD or those using cocaine. Such mice showed
hyperactivity, inattentiveness and lack of impulse control in a novel
environment. This behavior was measured by their ability to complete a
complicated maze that required the
Contact: Becky Levine
Duke University Medical Center