ArticleScientific reports2022
A role for cortical dopamine in the paradoxical calming effects of psychostimulants.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Methylphenidate reorganizes cortical hierarchy through dopaminergic modulation.Nature communications · 2025Trial
- Impact of childhood adversity on acute subjective effects of stimulant and opioid drugs: Evidence from placebo-controlled studies in healthy volunteers.Journal of psychopharmacology (Oxford, England) · 2024Trial
- The Effects of Tyrosine Hydroxylase Blockade in Mice Lacking the Norepinephrine Transporter (NET-KO Mice).International journal of molecular sciences · 2026Article
- Medication vs. Movement in ADHD: Interaction Between Medication and Physical Activity on Neurocognitive Functioning.Brain sciences · 2025Article
- Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.Clinical drug investigation · 2025Review
- A Common Cause of ADHD and Bipolar Disorder (BD).Bipolar disorders · 2025Article
- D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders.Molecular psychiatry · 2025Article
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction.Advances in neurobiology · 2025Review
- Factors associated with attention-deficit/hyperactivity disorder among Tunisian children.Frontiers in psychiatry · 2025Article
- Enhanced cognitive flexibility and phasic striatal dopamine dynamics in a mouse model of low striatal tonic dopamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models.Frontiers in psychiatry · 2024Review
- Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.Biomolecules · 2023Review
- From attention-deficit hyperactivity disorder to sporadic Alzheimer's disease-Wnt/mTOR pathways hypothesis.Frontiers in neuroscience · 2023Article
- Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats.Biomolecules · 2022Article
- Attention-deficit/hyperactive disorder updates.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psychostimulants have a paradoxical calming effect in the treatment of attention deficit hyperactivity disorder (ADHD), but their mechanism of action is unclear. Studies using dopamine (DA) transporter (DAT) knockout (KO) mice have suggested that the paradoxical calming effect of psychostimulants might occur through actions on serotonin (5-HT) neurotransmission. However, newer non-stimulant drugs, such as atomoxetine and guanfacine, suggest that targeting the norepinephrine (NE) system in the prefrontal cortex (PFC) might explain this paradoxical calming effect. Thus, we sought to clarify the mechanism of this paradoxical action of psychostimulants. Our ex vivo efflux experiments reveal that the NE transporter (NET) blocker desipramine elevates both norepinephrine (NE) and dopamine (DA), but not 5-HT levels, in PFC tissue slices from wild-type (WT) and DAT-KO, but not NET-KO mice. However, the 5-HT transporter (SERT) inhibitor fluoxetine elevates only 5-HT in all three genotypes. Systemic administration of desipramine or fluoxetine inhibits hyperactivity in DAT-KO mice, whereas local PFC infusion of desipramine alone produced this same effect. In contrast, pharmacological NE depletion and DA elevation using nepicastat also inhibits hyperactivity in DAT-KO mice. Together, these data suggest elevation of PFC DA and not NE or 5-HT, as a convergent mechanism for the paradoxical effects of psychostimulants observed in ADHD therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.