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Two Dopamine Receptors Are Key to Ritalin Activity

Research reported by scientists from the University of California-San Francisco (UCSF) has shown that, in a rat model, Ritalin (methylphenidate) boosts both the ability to focus on tasks and the speed of learning by increasing the activity of the neurotransmitter dopamine through mechanisms involving two distinct dopamine receptors in the amygdala region of the brain. "We found that a dopamine receptor, known as the D2 receptor, controls the ability to stay focused on a task--the well-known benefit of Ritalin," said Dr. Patricia Janak, co-senior author of the paper. "But we also discovered that another dopamine receptor, D1, underlies learning efficiency." "Since we now know that Ritalin improves behavior through two specific types of neurotransmitter receptors, the finding could help in the development of better targeted drugs, with fewer side effects, to increase focus and learning," said Dr. Antonello Bonci, the other co-senior author of the article. The research assessed the ability of rats to learn that they could get a sugar water reward when they received a signal--a flash of light and a sound. The scientists compared the behavior of animals receiving Ritalin with those that did not receive it, and found those receiving Ritalin learned much better. However, they also found that if they blocked the dopamine D1 receptors with drugs, Ritalin was unable to enhance learning. And if they blocked D2 receptors, Ritalin failed to improve focus. The experiments established the distinct role of each of the dopamine receptors in enabling Ritalin to enhance cognitive performance.

In addition, animals that performed better after Ritalin treatment showed enhanced synaptic plasticity in the amygdala. Enhanced synaptic plasticity is essentially increased efficiency of neural transmission due to strengthening of the communication between neurons where they meet at the synapse. The researchers confirmed this increased plasticity by measuring electrical activity in neurons in the amygdala after Ritalin treatment.

The research also confirmed that learning and focus were enhanced when Ritalin was administered to animals in doses comparable to those used therapeutically in children.

"By identifying the brain mechanisms underlying Ritalin's behavioral enhancements, we can better understand the action of Ritalin, as well as the properties governing brain plasticity," said the paper’s lead author, Dr. Kay Tye.

The new research was published online on March 7, 2010 in Nature Neuroscience. [Press release] [Nature Neuroscience abstract]