The DOI matches its Crossref record; 294 of the 294 references it cites were found in a registry or an index.
Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration
Abstract
The psychostimulants, D-amphetamine (D-AMP) and methylphenidate (MPH), are widely used to treat attention-deficit hyperactivity disorder (ADHD) in both children and adults. The purpose of this paper is to integrate results of basic and clinical research with stimulants in order to enhance understanding of the neuropharmacological mechanisms of therapeutic action of these drugs. Neurochemical, neurophysiological and neuroimaging studies in animals reveal that the facilitative effects of stimulants on locomotor activity, reinforcement processes, and rate-dependency are mediated by dopaminergic effects at the nucleus accumbens, whereas effects on delayed responding and working memory are mediated by noradrenergic afferents from the locus coeruleus (LC) to prefrontal cortex (PFC). Enhancing effects of the stimulants on attention and stimulus control of behavior are mediated by both dopaminergic and noradrenergic systems. In humans, stimulants appear to exert rate-dependent effects on activity levels, and primarily enhance the motor output, rather than stimulus evaluation stages of information-processing. Similarity of response of individuals with and without ADHD suggests that the stimulants do not target a specific neurobiological deficit in ADHD, but rather exert compensatory effects. Integration of evidence from pre-clinical and clinical research suggests that these effects may involve stimulation of pre-synaptic inhibitory autoreceptors, resulting in reduced activity in dopaminergic and noradrenergic pathways. The implications of these and other hypotheses for further pre-clinical and clinical research are discussed.
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“Authors of other reports suggest that more than 90% of patients will have a beneficial response to 1 of the psychostimulants if a range of medications from both the methylphenidate and amphetamine and/or dextroamphetamine classes are tried.147”
From Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents (2019) · cites this paper as [147]
In the citing paper
“First, LDX induces activation of the known dopaminergic and adrenergic receptors DA receptor 1A (DRD1), DA receptor 1B (DRD5), DRD2, ADRA2A, ADRA2B and alpha-2C adrenergic receptor (ADRA2C) [155, 158, 159], contributing to neurotransmission signalling.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [159]
In the citing paper
“The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5 [155, 158, 159], and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile [160].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [159]
In the citing paper
“The DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX [155, 158, 159].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [159]
In the citing paper
“Thus, by virtue of their DA and NE amplifying capacity (Kuczenski and Segal, 1997;Solanto, 1998), stimulants may enhance task-specific signaling in target neurons within specific circuits.”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Solanto, 1998
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Metadata
- Authors
- Solanto, M. V.
- Affiliations
- Long Island Jewish Medical Center (US)
- Corresponding author
- Solanto, Mary V
- ORCID
- Solanto, Mary V
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 94
- Issue
- 1
- Pages
- 127-152
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2098677721
- Semantic Scholar
- e90307547cfdc0caeea1fa7792a0985f5f82a807
- Cited by
- 677
- References
- 294
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 17 · 2019: 18 · 2018: 13 · 2017: 13 · 2016: 17 · 2015: 24 · 2014: 18 · 2013: 22 · 2012: 38
- FWCI
- 15.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- 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, psychostimulants, d-amphetamine, methylphenidate, dopaminergic system, noradrenergic system, nucleus accumbens, locus coeruleus, prefrontal cortex, working memory, rate-dependent effects, locomotor activity, reinforcement processes, compensatory mechanisms
- MeSH terms
- Adult, Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Brain, Child, Dextroamphetamine, Humans, Methylphenidate
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