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Methylphenidate works by increasing dopamine levels

Scott Gottlieb, New York

Methylphenidate works in the treatment of attention deficit hyperactivity disorder by increasing levels of dopamine in children's brains, according to a study reported in the Journal of Neuroscience (2001;21:121).

Previous research in animals and people had shown that methylphenidate (Ritalin) increases dopamine levels, but the studies involved injections of doses much higher than normally prescribed to children.

To see whether the smaller oral doses of methylphenidate that are usually prescribed to children have the same effects, the researchers, led by Dr Nora Volkow at the Brookhaven National Laboratory in Upton, New York, scanned the brains of 11 healthy men aged 20 to 40 using positron emission tomography to measure levels of dopamine in the brain striatum. One scanning session occurred after the men had taken methylphenidate, and the other took place after they had taken a placebo, which did not contain any drug.

About an hour after the men took methylphenidate, dopamine levels in their brains increased significantly. The drug seems to raise levels of the hormone by blocking the activity of dopamine transporters, which remove dopamine once it has been released.

Dopamine, a hormone that plays a role in feelings of pleasure, is also intimately involved with the motivational process, according to Dr Volkow. Dopamine decreases "background firing" rates and increases the signal to noise ratio in target neurones by increasing dopamine levels in the brain. As a result, the drug may improve attention and decrease distractibility in activities that normally do not hold the attention of children with attention deficit hyperactivity disorder.

For example, after taking methylphenidate, an arithmetic problem might become more interesting to a child who is normally turned off by maths, Dr Volkow said. "All of a sudden, it's not boring," she said.

Previous research has shown that some people with attention deficit hyperactivity disorder may have too many dopamine transporters, which results in low levels of dopamine in the brain. By blocking these transporters, methylphenidate seems to keep dopamine levels high enough for children not to lose interest.

The findings may also help to explain why methylphenidate, when used as recommended, is not addictive, said the researchers. The drug increases dopamine levelsas do many addictive drugs, including cocaine, alcohol, and amphetaminesbut the key difference may be the length of time that the drugs take to reach the brain.

The researchers said that a drug must reach the brain very quickly for it to become addictive. On average, it takes an oral dose of methylphenidate about an hour to have an effect on the brain, which prevents the drug from causing the "high" produced by most drugs that stimulate dopamine. Methylphenidate could become addictive, however, when tablets are crushed and then either snorted or injected, which allows the drug to reach the brain more rapidly.

(Credit: AP PHOTO) Christian Domenech, 9, who has attention deficit hyperactivity disorder