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Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder
Abstract
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.
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“and blunted dopamine release was associated with both greater symptoms of inattention and with greater drug liking (Volkow et al., 2007a; although see Rosa-Neto et al., 2005).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Rosa-Neto et al., 2005
In the citing paper
“One study in adolescent patients with ADHD found that oral methylphenidate-induced increases in dopamine concentrations in the right striatum were greater in patients showing poor performance on a computerized continuous performance test relative to high performing patients (Rosa-Neto et al., 2005).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Rosa-Neto et al., 2005
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Metadata
- Authors
- Rosa-Neto, P., Lou, H. C., Cumming, P., Pryds, O., Karrebaek, H., Lunding, J., & Gjedde, A.
- Affiliations
- Aarhus University (DK)
- Kennedy Center (DK)
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 25
- Issue
- 3
- Pages
- 868-876
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W1974649221
- Cited by
- 135
- References
- 67
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 12
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lundbeckfonden
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- attention deficit hyperactivity disorder, methylphenidate, striatal dopamine, dopamine D2/D3 receptors, [11C]raclopride, inattention, impulsivity, adolescents, continuous performance test, impulse control
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention, Attention Deficit Disorder with Hyperactivity, Child, Corpus Striatum, Dominance, Cerebral, Dopamine, Dose-Response Relationship, Drug, Drug Synergism, Female, Humans, Image Processing, Computer-Assisted, Impulsive Behavior, Male, Methylphenidate, Neuropsychological Tests, Pattern Recognition, Visual, Psychomotor Performance, Radioligand Assay, Reaction Time, Statistics as Topic, Treatment Outcome, Receptors, Dopamine D2, Raclopride, Positron-Emission Tomography, Receptors, Dopamine D3
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