Dopamine Role in ADHD May Explain Drug’s Efficacy

During the past several years, evidence has been mounting that the neurotransmitter dopamine may play a role not only in the causation of attention deficit/hyperactivity disorder (ADHD), but also in its treatment.

This finding suggests that a dopamine deficiency may underlie ADHD. Then Nora Volkow, M.D., a psychiatrist with Brookhaven National Laboratory in Upton, N.Y., and her colleagues found that intravenous injections of the drug most often prescribed to treat ADHD—methylphenidate (Ritalin)—increased dopamine levels in the brain. This result suggests that methylphenidate counters ADHD by increasing brain levels of dopamine.

And now Volkow, along with colleagues at Brookhaven and the State University of New York at Stony Brook, reported in the January 15 online issue of the Journal of Neuroscience that oral doses of methylphenidate also increase brain levels of dopamine. Since methylphenidate is usually given to ADHD patients in oral form, this finding is even stronger evidence that methylphenidate counters ADHD by raising brain levels of dopamine.

In this study, Volkow and her team used positron emission tomography (PET) to explore the effects of oral doses of methylphenidate on dopamine in the brains of 11 healthy young subjects. In essence, they gave the subjects a placebo, and then a radioactive substance that competed, in their brains, with endogenous dopamine for dopamine receptors. They measured the level of this radioactive substance in the subjects’ brains. Sometime later they gave the subjects methylphenidate, then the radioactive substance, and once again measured the level of the substance in the subjects’ brains. Then they compared the level of the radioactive substance given under the influence of the placebo with that given under the influence of methylphenidate. They found that the level was lower under the influence of the drug than under that of the placebo. This lower level of the radioactive substance in the drug state suggested that there was more dopamine in the subjects’ brains under the influence of methylphenidate than a placebo.

“This research begins to explain how methylphenidate works to treat ADHD,” said Alan Leshner, Ph.D., director of the National Institute on Drug Abuse in Bethesda, Md. Volkow agreed. For instance, she speculated that if a child with ADHD has a deficit of dopamine in the brain, and methylphenidate restores that level, then the extra dopamine may amplify dopamine activity between nerves and thus lead to less agitation and improved attention.

Aside from its possible role in the cause and treatment of ADHD, dopamine is known to control movement and to be involved in Parkinson’s disease; to influence motivation and modulate reward; to interact with drugs of abuse (Psychiatric News, April 21, 2000), and to be implicated in schizophrenia (see page xx).

The full text of the study, “Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain,” is posted on the Web at www.jneurosci.org. ▪