For more than seven decades, scientists have puzzled over the pharmacological mechanisms that somehow interact in children to reduce hyperactivity when they receive medications including methylphenidate — known by the trade names Ritalin, Concerta, and Methylin — and methamphetamine.

Since the mid-1950s, millions of children and adults have been prescribed stimulant medications to control attention deficit hyperactivity disorder (ADHD). But since the first experiment that gave an amphetamine drug to children diagnosed with behavioral problems, scientists have not known how stimulants work to control hyperactivity.

New research has identified a possible mechanism by which certain stimulants accomplish this paradoxical reduction of motor activity.

David Erlij, M.D., Ph.D., professor of physiology and pharmacology at SUNY Downstate, and fellow researchers have identified a network of nerve terminals in the rat brain where stimulation of dopamine D4 receptors depresses motor activity.

“This network is localized deep in the brain, in the basal ganglia and the thalamus,” said Erlij, “and its responses explain the reduction in motor activity caused by psychostimulants.”

The findings were published in a recent edition of the journal Neuropharmacology.

“When, in 1937, Dr. Charles Bradley administered Benzedrine to a group of children with hyperactivity and learning disorders and discovered that ’14 children responded in a spectacular fashion,’ a new era of psychopharmacology was inaugurated,” Erlij said.

“Bradley showed, for the first time, that taking a pill could successfully treat a behavioral abnormality. Eventually, this discovery led to the widespread use of psychostimulant drugs in the treatment of ADHD.”

“Despite their well established beneficial effects, it was not understood why psychostimulant drugs, which normally amplify the stimulatory responses of dopamine signals, reduce hyperactivity.

“Our results suggest that enhancing dopamine D4 transmission in the basal ganglia and the thalamus is likely part of the mechanism of the therapeutic effects of psychostimulants on ADHD.”

Erlij believes the therapeutic action of psychostimulants in ADHD occurs because the condition is caused by abnormalities of dopamine signaling in the brain. That is, when an individual has ADHD, the dopamine D4 receptor gene is abnormal.

Source: SUNY Downstate Medical Center