Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: Correlation with attentional deficit

Pedro Rosa Neto, Hans Lou, Paul Cumming, Ole Pryds, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

Perinatal anoxia/ischemia or premature birth increases the risk of developing attention deficit/hyperactivity disorder (ADHD). Brain imaging studies of idopathic ADHD reveal elevated dopamine transporter density in striatum of patients, predicting abnormal response to a challenge with methylphenidate in this population. We hypothesized that the severity of attention deficit in adolescents should correlate with the sensitivity to psychostimulant-evoked dopamine release. To test this hypothesis, we investigated six adolescent subjects (mean age 14.2 ± 2.4 yr) with documented birth trauma and/or low birth weight and a diagnosis of ADHD. Using positron emission tomography (PET), we measured the relative binding of [11C]raclopride to dopamine receptors in striatum, first in the baseline condition and again after methylphenidate challenge at a therapeutic dose for ADHD (0.3 mg/kg, p.o.) in order to map the altered dopamine release evoked by the psychostimulant challenge. Neuropsychological measurements of impulsivity and inattention were also performed. We found a positive correlation between commission errors and the methylphenidate-evoked decrease in [11C]raclopride binding, thought to reflect the balance of dopamine release and reuptake. The greater the decline in the [11C]raclopride binding, the greater the ability of methylphenidate to block the reuptake of dopamine. As the ability to block the reuptake depends on the relative dopamine concentration, the result suggests that the impulsivity in these adolescents is associated with abnormally low extracellular dopamine concentration.

Original languageEnglish (US)
Pages (from-to)434-439
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume965
DOIs
StatePublished - 2002

Keywords

  • Attention deficit/hyperactivity disorder
  • D2
  • Dopamine
  • Premature birth
  • Raclopride
  • Receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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