Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: correlation with attentional deficit.
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 [(11)C]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 [(11)C]raclopride binding, thought to reflect the balance of dopamine release and reuptake. The greater the decline in the [(11)C]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.
Rosa Neto
Pedro
P
PET Center, Arhus Kommunehospital, Nørrebrogade 44, Arhus, Denmark. pedro@pet.auh.dk
Lou
Hans
H
Cumming
Paul
P
Pryds
Ole
O
Gjedde
Albert
A
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008774:Methylphenidate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D020891:Raclopride / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine