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Cited by 146Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate

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Engert, Veronika, Pruessner, Jens·2008·Current Neuropharmacology
DOI 10.2174/157015908787386069PMC PMC2701285
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Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric condition characterized by severe impulsiveness, inattention and overactivity. Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, is one of the most frequently prescribed treatments for ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise neurochemical mechanisms of action are under debate. For the most part, MPH's influence on subcortical dopamine neurotransmission is thought to play a crucial role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate tonic dopamine while inhibiting phasic transmitter release in subcortical structures, leading to reduced postsynaptic receptor stimulation and psychomotor activation in response to salient stimuli. Volkow and colleagues [56] suggest that by amplifying a weak striatal dopamine signal, MPH increases the perception of a stimulus or task as salient. The enhanced interest for the task is thought to increase attention and improve performance. Recent animal studies have however shown that when administered at doses producing clinically relevant drug plasma levels and enhancing cognitive function, MPH preferentially activates dopamine and noradrenaline efflux within the prefrontal cortex relative to the subcortical structures [5]. Overall, we suggest that the delineated theories of MPH therapeutic action should not be discussed as exclusive. Studies are outlined that allow integrating the different findings and models.

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  • Lower DA levels in the PFC could lead to less motivation, resulting in inattention, and might also be the reason for promiscuous reward-seeking behaviours found in hyperactive-impulsive patients with ADHD.

    “This system is involved in motivation and reward/avoidance behaviours; in this sense, lower DA levels in the PFC could lead to less motivation, resulting in inattention. This might also be the reason for the promiscuous reward-seeking behaviours found in hyperactive-impulsive patients with ADHD [83].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [83]

    The Introduction links prefrontal dopamine to cognitive function, while the “Saliency Enhancing” Model links dopamine-mediated motivation to attention. But those passages concern different pathways: the paper does not say that low dopamine in the PFC reduces motivation or causes inattention, or that it explains promiscuous reward-seeking in hyperactive-impulsive ADHD. (LLM, conf=0.84)

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  • DAT-1 is a DA transporter whose function is the reuptake of extracellular DA in the synaptic space.

    “Moreover, DAT-1 is a DA transporter whose function is the reuptake of extracellular DA in the synaptic space [83].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [83]

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Authors
Engert, V., & Pruessner, J.
Affiliations
Douglas Mental Health University Institute (CA)
Corresponding author
Engert, Veronika
ORCID
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2008-12-01
Volume
6
Issue
4
Pages
322-328
ISSN
1570-159X (ISSN-L)
DOI
10.2174/157015908787386069
PMC
PMC2701285
OpenAlex
W2078736514
Cited by
146
References
12
Citations by year
2026: 4 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 8 · 2021: 16 · 2020: 15 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 5
FWCI
2.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Current Neuropharmacology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
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, methylphenidate, dopaminergic system, noradrenergic system, psychostimulants, dopamine signaling, norepinephrine, prefrontal cortex, striatal dopamine, mechanism of action, salience, attention

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