Methylphenidate hydrochloride (MP) is an effective treatment for attention-deficit/hyperactivity
disorder (ADHD), a common neurobehavioral disorder of childhood onset characterized
by inattention, hyperactivity, and distractibility. Methylphenidate hydrochloride
blocks the dopamine transporters (DAT), the main mechanism for removing dopamine (DA)
from the synapse, is believed to be involved in its therapeutic properties. However,
the mechanism(s) by which increases in DA improve symptomatology in ADHD are not completely
understood. Our studies of the dopaminergic effects of MP in the human brain using
positron emission tomography (PET) have shown that MP blocks DAT, and that extracellular
DA increases in proportion to the level of blockade and the rate of DA release (modulated
by DA cell firing). These DA increases are greater when MP is given concomitantly
with a salient stimulus than with a neutral stimulus, documenting the context dependency
of MP effects. Additionally, MP-induced increases in DA are associated with an enhanced
perception of the stimulus as salient. We postulate the MP’s therapeutic effects are
due in part to its ability to enhance the magnitude of DA increases induced by stimuli
that by themselves generate weak responses, enhancing their saliency and the attention
and interest they elicit. We postulate that these effects would improve school performance.
Key Words
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Article info
Publication history
Published online: January 13, 2005
Accepted:
November 1,
2004
Received in revised form:
October 19,
2004
Received:
June 10,
2004
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
