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Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration

Solanto, Mary V·1998·Behavioural Brain Research

DOI 10.1016/s0166-4328(97)00175-7

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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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Background
The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT1A receptor
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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)
DOI: 10.1016/s0166-4328(97)00175-7
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration

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