Catecholamine influences on dorsolateral prefrontal cortical networks

Biol Psychiatry. 2011 Jun 15;69(12):e89-99. doi: 10.1016/j.biopsych.2011.01.027. Epub 2011 Apr 13.


The symptoms of attention-deficit/hyperactivity disorder (ADHD) involve impairments in prefrontal cortical top-down regulation of attention and behavior. All current pharmacological treatments for ADHD facilitate catecholamine transmission, and basic research suggests that these compounds have prominent actions in the prefrontal cortex (PFC). The dorsolateral PFC is especially sensitive to levels of norepinephrine and dopamine, whereby either too little or too much markedly impairs PFC function. Recent physiological studies have shown that norepinephrine strengthens PFC network connectivity and maintains persistent firing during a working memory task through stimulation of postsynaptic α(2A)-adrenoceptors on PFC neurons. Conversely, dopamine acts at D1 receptors to narrow spatial tuning, sculpting network inputs to decrease noise (i.e., stabilization of the representation). The stimulant medications and atomoxetine appear to enhance PFC function by indirectly increasing these catecholamine actions through blockade of norepinephrine and/or dopamine transporters. In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α(2A)-receptors in the PFC, strengthening network connectivity. Stronger PFC regulation of attention, behavior, and emotion likely contributes to the therapeutic effects of these medications for the treatment of ADHD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Agonists / therapeutic use
  • Animals
  • Arousal / physiology
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Catecholamines / physiology*
  • Cognition / physiology
  • Guanfacine / pharmacology
  • Guanfacine / therapeutic use
  • Humans
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Methylphenidate / pharmacology
  • Methylphenidate / therapeutic use
  • Models, Neurological
  • Neural Pathways / physiology*
  • Prefrontal Cortex / physiology*
  • Propylamines / pharmacology
  • Propylamines / therapeutic use
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-Agonists
  • Catecholamines
  • Propylamines
  • Methylphenidate
  • Guanfacine
  • Atomoxetine Hydrochloride