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The Roles of Dopamine and Noradrenaline in the Pathophysiology and Treatment of Attention-Deficit/Hyperactivity Disorder
Abstract
Through neuromodulatory influences over fronto-striato-cerebellar circuits, dopamine and noradrenaline play important roles in high-level executive functions often reported to be impaired in attention-deficit/hyperactivity disorder (ADHD). Medications used in the treatment of ADHD (including methylphenidate, dextroamphetamine and atomoxetine) act to increase brain catecholamine levels. However, the precise prefrontal cortical and subcortical mechanisms by which these agents exert their therapeutic effects remain to be fully specified. Herein, we review and discuss the present state of knowledge regarding the roles of dopamine (DA) and noradrenaline in the regulation of corticostriatal circuits, with a focus on the molecular neuroimaging literature (both in ADHD patients and in healthy subjects). Recent positron emission tomography evidence has highlighted the utility of quantifying DA markers, at baseline or following drug administration, in striatal subregions governed by differential cortical connectivity. This approach opens the possibility of characterizing the neurobiological underpinnings of ADHD (and associated cognitive dysfunction) and its treatment by targeting specific neural circuits. It is anticipated that the application of refined and novel positron emission tomography methodology will help to disentangle the overlapping and dissociable contributions of DA and noradrenaline in the prefrontal cortex, thereby aiding our understanding of ADHD and facilitating new treatments.
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“Deficiencies in catecholamines such as NE and DA [75, 79, 80] or dysregulation of such NTs, which are essential for normal brain function, including executive and attentional functions [33], are among the causing physiological alterations that have been reported to explain ADHD development.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [79]
In the citing paper
“NE-mediated signal transduction speed and duration are affected by NE transporter (NET) protein, as it is involved in NE reuptake [79].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [79]
In the citing paper
“NE, also known as noradrenaline (NA), is an important NT in behaviour control, playing a key role in high-level cognitive processes such as working memory and inhibitory response, which appear to be disrupted in ADHD [79], producing irritability and anxiety [85].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [79]
In the citing paper
“Deficits in certain kinds of attention are relevant to ADHD and other neurological disorders associated with dopamine deficiency (Del Campo et al., 2011).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Del Campo et al., 2011
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Metadata
- Authors
- del Campo, N., Chamberlain, S. R., Sahakian, B. J., & Robbins, T. W.
- Affiliations
- University of Cambridge (GB)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 69
- Issue
- 12
- Pages
- e145-e157
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2025431637
- Cited by
- 685
- References
- 129
- Citations by year
- 2026: 61 · 2025: 65 · 2024: 57 · 2023: 49 · 2022: 51 · 2021: 46 · 2020: 43 · 2019: 41 · 2018: 36 · 2017: 31 · 2016: 32 · 2015: 45 · 2014: 44 · 2013: 32 · 2012: 43
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Gates Cambridge Trust
- Wellcome Trust
- Medical Research Council
- 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, dopamine, norepinephrine, catecholamines, executive function, corticostriatal circuits, prefrontal cortex, striatum, positron emission tomography, methylphenidate, d-amphetamine, atomoxetine, neuromodulation, ADHD treatment
- MeSH terms
- Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Corpus Striatum, Dopamine, Humans, Neural Pathways, Norepinephrine, Prefrontal Cortex, Positron-Emission Tomography
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