The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder

Biol Psychiatry. 2011 Jun 15;69(12):e145-57. doi: 10.1016/j.biopsych.2011.02.036. Epub 2011 May 6.


Through neuromodulatory influences over fronto-striato-cerebellar circuits, dopamine and noradrenaline play important roles in high-level executive functions often reported to be impaired in attention-deficit/hyperactivity disorder (ADHD). Medications used in the treatment of ADHD (including methylphenidate, dextroamphetamine and atomoxetine) act to increase brain catecholamine levels. However, the precise prefrontal cortical and subcortical mechanisms by which these agents exert their therapeutic effects remain to be fully specified. Herein, we review and discuss the present state of knowledge regarding the roles of dopamine (DA) and noradrenaline in the regulation of corticostriatal circuits, with a focus on the molecular neuroimaging literature (both in ADHD patients and in healthy subjects). Recent positron emission tomography evidence has highlighted the utility of quantifying DA markers, at baseline or following drug administration, in striatal subregions governed by differential cortical connectivity. This approach opens the possibility of characterizing the neurobiological underpinnings of ADHD (and associated cognitive dysfunction) and its treatment by targeting specific neural circuits. It is anticipated that the application of refined and novel positron emission tomography methodology will help to disentangle the overlapping and dissociable contributions of DA and noradrenaline in the prefrontal cortex, thereby aiding our understanding of ADHD and facilitating new treatments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Brain Mapping / methods
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / therapeutic use
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology
  • Dopamine / physiology*
  • Humans
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Norepinephrine / physiology*
  • Positron-Emission Tomography / methods*
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology


  • Central Nervous System Stimulants
  • Dopamine
  • Norepinephrine