Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on Hyperactivity
Abstract
The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.
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Mice lacking the DAT gene display markedly increased levels of DA in the mesolimbic system and striatum, resulting in hyperlocomoter behaviors and deficits in PPI.
“Mice lacking the DAT gene display markedly increased levels of DA in the mesolimbic system and striatum [373], that results in hyperlocomoter behaviors [373,374] and also deficits in PPI [375,376].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [374]
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- Authors
- Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Levin, E. D., Jaber, M., & Caron, M. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jaber, Mohamed
- Caron, Marc G.
- ORCID
- Venue
- Science
- Published
- 1999-01-15
- Volume
- 283
- Issue
- 5400
- Pages
- 397-401
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2042123414
- Cited by
- 885
- References
- 6
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 24 · 2017: 24 · 2016: 17 · 2015: 23 · 2014: 44 · 2013: 32 · 2012: 26
- FWCI
- 31.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 40159)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serotonin, psychostimulants, hyperactivity, attention deficit hyperactivity disorder, hyperkinetic disorder, dopamine transporter knockout mice, dopaminergic tone, novel environment, spatial cognition, locomotion, serotonergic neurotransmission
- MeSH terms
- Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Behavior, Animal, Carrier Proteins, Corpus Striatum, Dopamine, Fluoxetine, Humans, Hyperkinesis, Membrane Glycoproteins, Mice, Inbred C57BL, Motor Activity, Nerve Tissue Proteins, Synaptic Transmission, Serotonin, Selective Serotonin Reuptake Inhibitors, Mice, Knockout, Maze Learning, Membrane Transport Proteins, Symporters, Dopamine Plasma Membrane Transport Proteins, Norepinephrine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Mice
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