Study Reveals How ADHD Drugs Work

The University of Wisconsin, Madison, issued an announcement about newresearch findings: Here's the announcement:

Although millions depend on medications such as Ritalin to quellsymptoms of attention deficit hyperactivity disorder (ADHD), scientistshave struggled to pinpoint how the drugs work in the brain.But new work at the University of Wisconsin-Madison is now starting toclear up some of the mystery. Writing in the journal BiologicalPsychiatry, UW-Madison researchers report that ADHD drugs primarilytarget the prefrontal cortex (PFC), a region of the brain that isassociated with attention, decision-making and an individual'sexpression of personality.The finding could prove invaluable in the search for new ADHDtreatments, and comes amidst deep public concern over the widespreadabuse of existing ADHD medicines."There's been a lot of concern over giving a potentially addictive drugto a child (with ADHD)," says lead author Craig Berridge, a UW-Madisonprofessor of psychology. "But in order to come up with a better drug, wemust first know what the existing drugs do."A behavioral disorder that afflicts both children and adults, ADHD ismarked by hyperactivity, impulsivity and an inability to concentrate.The National Institute of Mental Health estimates that 2 millionchildren in the U.S. suffer from the condition, with between 30 to 70percent of them continuing to exhibit symptoms in their adult years.Despite public anxiety over the treatment of a behavioral condition withdrugs, doctors have continued to prescribe meds like Adderall, Ritalinand Dexedrine because - quite simply - they work better than anything else.ADHD drugs fall into a class of medications known as stimulants. ADHDstimulants boost levels of two neurotransmitters, or chemical messengersin the brain, known as dopamine and norepinephrine. Dopamine is thoughtto play a role in memory formation and the onset of addictive behaviors,while norepinephrine has been linked with arousal and attentiveness.Berridge notes that scientists have learned little about how ADHD drugswork because past studies have primarily examined the effects of themedicines at high doses. High-dose stimulants can cause dramatic spikesin neurotransmitter levels in the brain, which can in turn impairattention and heighten the risk of developing addiction."It is surprising that no one was looking at low-dose (ADHD) drugsbecause we know that the drugs are most effective only at low doses,"says Berridge. "So we asked the natural question: what are these drugsdoing at clinically relevant doses?"To answer that question, Berridge and his team monitoredneurotransmitter levels in three different brain regions thought to betargeted by ADHD drugs: the PFC and two smaller brain areas known as theaccumbens which has been linked with processing "rewards," and themedial septum, which has been implicated in arousal and movement.Working with rats, the researchers conducted laboratory and behavioraltests to ensure that animal drug doses were functionally equivalent todoses prescribed in humans. Then, using a type of brain probe - aprocess known as microdialysis - the UW-Madison team measuredconcentrations of dopamine and norepinephrine in the three differentbrain areas, both in the presence and absence of low-dose ADHD stimulants.Under the influence of ADHD drugs, dopamine and norepinephrine levelsincreased in the rats' PFC. Levels in the accumbens and medial septum,however, remained much the same, the scientists found."Our work provides pretty important information on the importance oftargeting the PFC when treating ADHD," says Berridge, "In particular ittells us that if we want to produce new ADHD drugs, we need to target[neurotransmitter] transmission in the PFC."In the future, Berridge and his colleagues plan to look deeper withinthe PFC to gain more detailed insights into how ADHD medicines act onnerves to enhance cognitive ability.Other contributors to the study include UW-Madison co-authors DavidDevilbiss, Matthew Andrzejewski, Ann Kelley, Brooke Schmeichel,Christina Hamilton and Robert Spencer, and Yale Medical Schoolresearcher Amy Arnsten.