Cited by 26Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

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From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD

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Parlatini, Valeria, Bellato, Alessio, Murphy, Declan, Cortese, Samuele·2024·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2024.105841

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Abstract

Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

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Methylphenidate Decreased the Amount of Glucose Needed by the Brain to Perform a Cognitive Task
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Comparative Effects of Methylphenidate and Mixed Salts Amphetamine on Height and Weight in Children With Attention-Deficit/Hyperactivity Disorder
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Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder
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The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice
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MR imaging of the effects of methylphenidate on brain structure and function in Attention-Deficit/Hyperactivity Disorder
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Trace Amine-Associated Receptors as Emerging Therapeutic Targets
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Neurobiology of ADHD: A Review
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Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette's disorder
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Neuroimaging and ADHD: fMRI, PET, DTI Findings, and Methodological Limitations
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Reward processing in male adults with childhood ADHD—a comparison between drug-naïve and methylphenidate-treated subjects
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Long-Term Effects of Methylphenidate on Neural Networks Associated With Executive Attention in Children With ADHD: Results From a Longitudinal Functional MRI Study
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Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory
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Methylphenidate Normalizes Resting-State Brain Dysfunction in Boys With Attention Deficit Hyperactivity Disorder
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Dopaminergic dysfunction in attention deficit hyperactivity disorder (ADHD), differences between pharmacologically treated and never treated young adults: A 3,4-dihdroxy-6-[18F]fluorophenyl-l-alanine PET study
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Dopamine D4Receptors Regulate AMPA Receptor Trafficking and Glutamatergic Transmission in GABAergic Interneurons of Prefrontal Cortex
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The Effects of Stimulant Medication on Working Memory Functional Connectivity in Attention-Deficit/Hyperactivity Disorder
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Methylphenidate Exerts Dose-Dependent Effects on Glutamate Receptors and Behaviors
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Imaging the norepinephrine transporter in humans with (S,S)-[11C]O-methyl reboxetine and PET: problems and progress
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Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD
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The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT1A receptor
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White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with Attention-Deficit/Hyperactivity Disorder
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Positron emission tomography neuroimaging for a better understanding of the biology of ADHD
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Methylphenidate and atomoxetine normalise fronto-parietal underactivation during sustained attention in ADHD adolescents
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The role of glutamate receptors in attention‐deficit/hyperactivity disorder: From physiology to disease
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Differential regulation of psychostimulant‐induced gene expression of brain derived neurotrophic factor and the immediate‐early geneArcin the juvenile and adult brain
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The Norepinephrine Transporter in Attention-Deficit/Hyperactivity Disorder Investigated With Positron Emission Tomography
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Changes in plasma Brain-derived neurotrophic factor (BDNF) levels induced by methylphenidate in children with Attention deficit–hyperactivity disorder (ADHD)
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Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate treatment in adults with attention deficit hyperactivity disorder
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Systematic Review: Medication Effects on Brain Intrinsic Functional Connectivity in Patients With Attention-Deficit/Hyperactivity Disorder
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Sensation‐to‐cognition cortical streams in attention‐deficit/hyperactivity disorder
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Homeostatic regulation of glutamatergic transmission by dopamine D 4 receptors
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Neurofunctional Effects of Methylphenidate and Atomoxetine in Boys with Attention-Deficit/Hyperactivity Disorder During Time Discrimination
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5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats
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The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD
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Animal models of attention‐deficit hyperactivity disorder (ADHD)
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Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET
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“…differences in the NET binding potential between adults with ADHD and neurotypical controls in the thalamus and cerebellum; as well as genotype-dependent associations between cerebellar NET binding potential and hyper-activity/impulsivity in the ADHD group (Sigurdardottir et al., 2016).”
Background
Role of neurotrophic factors in attention deficit hyperactivity disorder
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Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD
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., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.349 · Cited by 49 · cited 1×
“This has been noted to be reduced in individuals with ADHD (Forssberg et al., 2006, Volkow et al., 2001, Volkow et al., 2007a), although this was not confirmed by all studies (Cherkasova et al., 2014).”
Differential effects of methylphenidate and atomoxetine on intrinsic brain activity in children with attention deficit hyperactivity disorder
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Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life
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Self-citation
Novel pharmacological targets for GABAergic dysfunction in ADHD
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Parlatini, 2023, White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review of 129 diffusion imaging studies with meta-analysis, Mol. Psychiatry, 10.1038/s41380-023-02173-1 · DOI
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Authors: Parlatini, V., Bellato, A., Murphy, D., & Cortese, S.
Affiliations: King's College London (GB)
University of Nottingham (GB)
Corresponding author: Parlatini, Valeria
ORCID: Parlatini, Valeria
Bellato, Alessio
Murphy, Declan
Cortese, Samuele
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2024-09
Volume: 164
Pages: 105841
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2024.105841
OpenAlex: W4401306218
Cited by: 26
References: 230
Citations by year: 2026: 10 · 2025: 15 · 2024: 1
FWCI: 2.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion, cc-by)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: iMinds
British Association for Psychopharmacology
Aims2Cure (AIMS-2-TRIALS, 115300, 777394)
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, stimulant medication, pharmacodynamics, dopamine signaling, brain networks, default mode network, salience, long-term treatment outcomes, predictors of treatment response
MeSH terms: Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Brain, Humans, Nerve Net, Neurons

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From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD

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