Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder

Neuroimage. 2005 Apr 15;25(3):868-76. doi: 10.1016/j.neuroimage.2004.11.031.


Abnormal central dopamine (DA) neurotransmission has been implicated in the impulsivity, inattention, and hyperactivity of attention deficit hyperactivity disorder (ADHD). We hypothesized that a pharmacological challenge with methylphenidate (MP) at a therapeutic dose increases extracellular DA concentrations in proportion to the severity of these specific ADHD symptoms. To test this hypothesis, we measured by PET the effect of acute challenge with MP on the availability of striatal binding sites for [11C]raclopride (pB), an index of altered interstitial DA concentration, in nine unmedicated adolescents (1 female, 8 males; age 13.7 +/- 1.8 years) with a current diagnosis of ADHD. We estimated the pB of [11C]raclopride for brain dopamine D2/3 receptors first in a baseline resting condition, and again after an acute challenge with MP (0.3 mg/kg, p.o.), and calculated the percentage change in (%DeltapB) in left and right striatum. On another day, measurements of impulsivity and inattention were performed using a computerized continuous performance test. There was a significant correlation between the magnitude of %DeltapB in the right striatum and the severity of inattention and impulsivity. MP-evoked %DeltapB correlated with standard scores for impulse control (r = 0.68; P = 0.02), attention (r = 0.81; P = 0.005), information processing (r = 0.66; P = 0.02), and consistency of attention, or variability (r = 0.60; P = 0.04). In conclusion, the results link inattention and impulsivity with sensitivity of brain DA receptor availability to an MP challenge, corroborating the hypothesis that MP serves to potentiate decreased DA neurotransmission in ADHD.

Publication types

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

MeSH terms

  • Adolescent
  • Attention / drug effects
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging*
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Central Nervous System Stimulants* / therapeutic use
  • Child
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Dominance, Cerebral / physiology
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Humans
  • Image Processing, Computer-Assisted*
  • Impulsive Behavior / diagnostic imaging*
  • Impulsive Behavior / drug therapy
  • Male
  • Methylphenidate* / therapeutic use
  • Neuropsychological Tests
  • Pattern Recognition, Visual / drug effects
  • Positron-Emission Tomography*
  • Psychomotor Performance / drug effects
  • Raclopride
  • Radioligand Assay
  • Reaction Time / drug effects
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D3
  • Statistics as Topic
  • Treatment Outcome


  • Central Nervous System Stimulants
  • DRD3 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Methylphenidate
  • Raclopride
  • Dopamine