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

TY - JOUR

T1 - Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: correlation with attentional deficit

AU - Rosa, Pedro

AU - Lou, Hans

AU - Cumming, Paul

AU - Pryds, Ole

AU - Gjedde, Albert

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12105118

SN - 0077-8923

VL - 965

SP - 434

EP - 439

JO - Annals of The Lyceum of Natural History of New York

JF - Annals of The Lyceum of Natural History of New York

ER -