A multinational collaboration between researchers from Spain, Mexico and Argentina revealed, that mice could provide an insight into how specific receptor subtypes in the brain could be responsible in increasing a person’s risk for attention-deficit hyperactivity disorder (ADHD), and help explaining how stimulants work to treat symptoms of ADHD. The research was conducted by the Intramural Research Program (IRP) at the National Institute on Drug Abuse (NIDA), which is a part of the National Institutes of Health.

ADHD is associated with dysfunction of the dopamine D4 receptor subtype in addition to other disorders characterized by decreased impulse control, including drug abuse. One subtype variant of the dopamine D4 receptor, called D4.7, that has been poorly understood until now, was of particular interest to the researchers because of its higher occurrence in ADHD diagnosed patients.

Researchers inserted three variants of the dopamine D4 receptor into cells and into mice, to evaluate differences in biological activities. The study was published in today’s Molecular Psychiatry and revealed, that unlike its D4.2 and D4.4 counterparts, the D4.7 variant was not able to interact with the short version of the dopamine type 2 (DS2) receptor to reduce glutamate release in the brain’s region that is linked to impulsivity and ADHD symptoms in humans.

NIDA Director Dr. Nora D. Volkow said,

“Although previous studies have shown that dysfunctional dopamine D4 receptors are implicated in ADHD, this is the first study to show how this genetic difference might translate into functional deficits seen with this disorder,” continuing, “Further research is needed to explore how this deficient interaction between receptors might be remedied, which could then lead to new medications for the treatment of ADHD.”

Children with ADHD have difficulty in paying attention and controlling impulsive behaviors. They may be overly active which often results in poor school performance and social difficulties and also have an increased risk for substance use disorders especially if their symptoms remain untreated.

ADHD is the most commonly diagnosed neurobehavioral childhood disorder with numbers of diagnosed children continuing to rise. The National Survey of Children’s Health by the Center of Disease Control showed, that from 2003 until 2007 the number of ADHD cases identified by parents of children between the ages of 4 to 17 years rose to 21.8 percent. Nearly one in 10 children of this age group was at some point diagnosed with ADHD by 2007.

66.3% percent of children currently diagnosed with ADHD received medication for their disorder. The most widely used treatment for ADHD is psychostimulant medication, but although these medicines alleviate some of the symptoms in ADHD, it is uncertain how these compounds act within the brain to do so.

Dr. Sergi Ferre, leading author of the study, said,

“Our results suggest that psychostimulants might reduce glutamate release by amplifying this D4/D2S interaction. These results might also explain why these medications are less efficient in patients with the D4.7 variant.”

The study was the result of a multinational collaboration between researchers at the NIDA IRP, institutes in Spain (the University of Barcelona, the Autonomous University of Barcelona and the University of Navarra), Mexico (the National Polytechnic Institute), and Argentina (the National Council of Scientific and Technical Research). For more information please visit: http://www.nature.com/mp/index.html.

More information on the use of stimulants to treat ADHD can be found here.

Link to further information on ADHD symptoms, its causes, treatments and how to get help and cope with the disorder.

Written by Petra Rattue