Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD
Open accessAbstract
Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.
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In a PET study, more pronounced reductions in amphetamine-induced reductions in striatal [11C]raclopride binding were associated with worse response inhibition, and those with ADHD had the highest-magnitude reductions.
“In a PET study of treatment-naive men with ADHD and men without ADHD, more pronounced reductions in AMP-induced reductions in striatal [11C]raclopride binding were associated with worse response inhibition, and those with ADHD had the highest-magnitude reductions and AMP-induced reductions in striatal [11C]raclopride binding (209).”
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“…n/a 21.32 n/a 20.63 n/a p.o. 1 hr 0.3 mg/kg Casey et al. (2014) Biological Psychiatry (n = 17) 9.91 2.77 11.78 2.63 14.93 2.95 p.o. 1 hr 0.3 mg/kg Cherkasova et al. (2014) Neuropsychopharmacology (n = 18) 0 n/a 3.25 n/a 12.34 n/a p.o. 1 hr 0.3 mg/kg Casey et al. (2013) Journal of Neuroscience (n…”
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“In addition to D2/3R deficits, both motor impulsive individuals [44,45] and novelty-seekers [46,47] also exhibit a heightened release of striatal DA in response to psychostimulants, an effect that has been related to the subjective “high” and euphoria experienced by healthy subjects to the drug [48,49].”
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- Authors
- Cherkasova, M. V., Faridi, N., Casey, K. F., O'Driscoll, G. A., Hechtman, L., Joober, R., Baker, G. B., Palmer, J., Dagher, A., Leyton, M., & Benkelfat, C.
- Affiliations
- McGill University (CA)
- University of Alberta (CA)
- Corresponding author
- Benkelfat, Chawki
- Venue
- Neuropsychopharmacology
- Published
- 2013-12-30
- Volume
- 39
- Issue
- 6
- Pages
- 1498-1507
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3988554
- OpenAlex
- W2080032371
- Cited by
- 49
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 3
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (77728)
- 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, dopamine release, striatum, response inhibition, neurocognitive function, treatment-naive adults, impulsivity, dopamine signaling
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Corpus Striatum, Dextroamphetamine, Dopamine, Humans, Inhibition, Psychological, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Radionuclide Imaging, Task Performance and Analysis, Dopamine Antagonists, Dopamine Uptake Inhibitors, Raclopride, Executive Function
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