Methylphenidate‐Evoked Potentiation of Extracellular Dopamine in the Brain of Adolescents with Premature Birth: Correlation with Attentional Deficit
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 [(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.
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Clinical doses of methylphenidate in adults and adolescents increased extrasynaptic levels of dopamine in the striatum due to potent blockade of dopamine transporters.
“Studies using positron emission tomography show that clinical doses of methylphenidate in adults (Volkow et al., 2002) and adolescents (Neto et al., 2002) increased (rather than decreased, as proposed by some theories) extrasynaptic levels of dopamine in the striatum due to potent blockade of dopamine transporters”
From Effects of Stimulant Medication on Growth Rates Across 3 Years in the MTA Follow-up (2007) · cites this paper as Neto et al., 2002
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- Authors
- NETO, P. R., LOU, H., CUMMING, P., PRYDS, O., & GJEDDE, A.
- Affiliations
- Aarhus Municipality (DK)
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2002-06
- Volume
- 965
- Issue
- 1
- Pages
- 434-439
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2157406338
- Cited by
- 54
- References
- 16
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 2 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, extracellular dopamine, dopamine transporter, striatum, psychostimulant sensitivity, impulsivity, inattention, preterm birth, low birth weight, adolescents, dopamine reuptake
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Brain, Carbon Radioisotopes, Dopamine, Extracellular Space, Humans, Infant, Newborn, Infant, Premature, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Tomography, Emission-Computed, Raclopride, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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