The prefrontal cortex guides behaviors, thoughts, and feelings using representational
knowledge, i.e., working memory. These fundamental cognitive abilities subserve the
so-called executive functions: the ability to inhibit inappropriate behaviors and
thoughts, regulate our attention, monitor our actions, and plan and organize for the
future. Neuropsychological and imaging studies indicate that these prefrontal cortex
functions are weaker in patients with attention-deficit/hyperactivity disorder and
contribute substantially to attention-deficit/hyperactivity disorder symptomology.
Research in animals indicates that the prefrontal cortex is very sensitive to its
neurochemical environment and that small changes in catecholamine modulation of prefrontal
cortex cells can have profound effects on the ability of the prefrontal cortex to
guide behavior. Optimal levels of norepinephrine acting at postsynaptic α-2A-adrenoceptors
and dopamine acting at D1 receptors are essential to prefrontal cortex function. Blockade
of norepinephrine α-2-adrenoceptors in prefrontal cortex markedly impairs prefrontal
cortex function and mimics most of the symptoms of attention-deficit/hyperactivity
disorder, including impulsivity and locomotor hyperactivity. Conversely, stimulation
of α-2-adrenoceptors in prefrontal cortex strengthens prefrontal cortex regulation
of behavior and reduces distractibility. Most effective treatments for attention-deficit/hyperactivity
disorder facilitate catecholamine transmission and likely have their therapeutic actions
by optimizing catecholamine actions in prefrontal cortex.
Key Words
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Article info
Publication history
Published online: October 21, 2004
Accepted:
August 31,
2004
Received in revised form:
August 9,
2004
Received:
June 4,
2003
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
