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ADD IN THE NEWS |
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Study reveals how ADHD drugs work in
brain |
University of
Wisconsin-Madison
MADISON
Although millions depend on
medications such as Ritalin to quell symptoms of attention deficit
hyperactivity disorder (ADHD), scientists have struggled to pinpoint
how the drugs work in the brain.
But new work at the University of Wisconsin-Madison is now starting
to clear up some of the mystery. Writing in the journal Biological
Psychiatry, UW-Madison researchers report that ADHD drugs primarily
target the prefrontal cortex (PFC), a region of the brain that is
associated with attention, decision-making and an individual's
expression of personality.
The finding could prove invaluable in the search for new ADHD
treatments, and comes amidst deep public concern over the widespread
abuse of existing ADHD medicines.
"There's been a lot of concern over giving a potentially addictive
drug to a child [with ADHD]," says lead author Craig Berridge, a
UW-Madison professor of psychology. "But in order to come up with a
better drug we must first know what the existing drugs do."
A behavioral disorder that afflicts both children and adults, ADHD
is marked by hyperactivity, impulsivity and an inability to
concentrate. The National Institute of Mental Health estimates that
2 million children in the U.S. suffer from the condition, with
between 30 to 70 percent of them continuing to exhibit symptoms in
their adult years.
Despite public anxiety over the treatment of a behavioral condition
with pharmacological drugs, doctors have continued to prescribe meds
like Adderall, Ritalin and Dexedrine because - quite simply - they
work better than anything else.
ADHD drugs fall into a class of medications known as stimulants.
ADHD stimulants boost levels of two neurotransmitters, or chemical
messengers in the brain, known as dopamine and norepinephrine.
Dopamine is thought to 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
drugs work because past studies have primarily examined the effects
of the medicines at high doses. High-dose stimulants can cause
dramatic spikes in neurotransmitter levels in the brain, which can
in turn impair attention and heighten the risk of developing
addiction.
"It is surprising that no one was looking at low-dose [ADHD] drugs
because we know that the drugs are most effective only at low
doses," says Berridge. "So we asked the natural question: what are
these drugs doing at clinically relevant doses?"
To answer that question, Berridge and his team monitored
neurotransmitter levels in three different brain regions thought to
be targeted by ADHD drugs: the PFC and two smaller brain areas known
as the accumbens which has been linked with processing "rewards,"
and the medial septum, which has been implicated in arousal and
movement.
Working with rats, the researchers conducted laboratory and
behavioral tests to ensure that animal drug doses were functionally
equivalent to doses prescribed in humans. Then, using a type of
brain probe - a process known as microdialysis - the UW-Madison team
measured concentrations of dopamine and norepinephrine in the three
different brain areas, both in the presence and absence of low-dose
ADHD stimulants.
Under the influence of ADHD drugs, dopamine and norepinephrine
levels increased 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 of
targeting the PFC when treating ADHD," says Berridge, "In particular
it tells 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
within the PFC to gain more detailed insights into how ADHD meds act
on nerves to enhance cognitive ability.
Other researchers who contributed to the study include UW-Madison
co-authors David Devilbiss, Matthew Andrzejewski, Ann Kelley, Brooke
Schmeichel, Christina Hamilton and Robert Spencer, and Yale Medical
School researcher Amy Arnsten. |
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