ArticleBiological psychiatry2014
Methylphenidate exerts dose-dependent effects on glutamate receptors and behaviors.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04964427 (The Effects of Methylphenidate), which is not on this map. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects of Methylphenidate (MPH) and Non-invasive Brain Stimulation (tDCS) on Inhibitory Control Children With Attention-Deficit/Hyperactivity Disorder (ADHD)
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studies.Molecular psychiatry · 2022Pooled it
- Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures.Molecular psychiatry · 2019Pooled it
- Dose-Dependent Effects of Catecholaminergic Modulation on Interference Control: Role of Baseline GABA and Glx in Cortico-Subcortical Networks.Human brain mapping · 2025Trial
- Aprepitant's neuroprotective effects on methylphenidate-induced biochemical/mitochondrial dysfunction, neuroinflammation, and mood-related behavior alterations.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Chronic Co-administration of Methylphenidate and Fluoxetine Reduces Striatal NMDA Receptor Binding in Adolescent Rats.Neurochemical research · 2026Article
- Article
- GABA and Glx levels in cortico-subcortical networks predict catecholaminergic effects on response inhibition.Journal of psychopharmacology (Oxford, England) · 2025Article
- Methylphenidate Exposing During Neurodevelopment Alters Amino Acid Profile, Astrocyte Marker and Glutamatergic Excitotoxicity in the Rat Striatum.Neurotoxicity research · 2024Article
- Learning and Memory Impairments With Attention-Deficit/Hyperactivity Disorder.Physiological research · 2024Review
- Chronic Methylphenidate Effects on Brain Gene Expression: An Exploratory Review.Psychology research and behavior management · 2024Review
- The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.Molecular psychiatry · 2024Article
- Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis.International journal of molecular sciences · 2023Review
- Role of environmental enrichment on social interaction, anxiety, locomotion, and memory in Wistar rats under chronic methylphenidate intake.Frontiers in behavioral neuroscience · 2023Article
- Psychosis Induced by Methylphenidate in Children and Young Patients With Attention-Deficit Hyperactivity Disorder.Cureus · 2023Review
- Kainate receptor subunit 1 (GRIK1) risk variants and GRIK1 deficiency were detected in the Indian ADHD probands.Scientific reports · 2022Article
- Therapeutic Approaches for ADHD by Developmental Stage and Clinical Presentation.International journal of environmental research and public health · 2022Review
- Adenosine AMolecular neurobiology · 2022Article
- Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner.Frontiers in pharmacology · 2022Article
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.Journal of clinical medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMethylphenidate (MPH), a psychostimulant drug used to treat attention-deficit/hyperactivity disorder, produces the effects of increasing alertness and improving attention. However, misuse of MPH has been associated with an increased risk of aggression and psychosis. We sought to determine the molecular mechanism underlying the complex actions of MPH.
methodsAdolescent (4-week-old) rats were given one injection of MPH at different doses. The impact of MPH on glutamatergic signaling in pyramidal neurons of prefrontal cortex was measured. Behavioral changes induced by MPH were also examined in parallel.
resultsAdministration of low-dose (.5 mg/kg) MPH selectively potentiated N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) via adrenergic receptor activation, whereas high-dose (10 mg/kg) MPH suppressed both NMDAR-mediated and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated EPSCs. The dual effects of MPH on EPSCs were associated with bidirectional changes in the surface level of glutamate receptor subunits. Behavioral tests also indicated that low-dose MPH facilitated prefrontal cortex-mediated temporal order recognition memory and attention. Animals injected with high-dose MPH exhibited significantly elevated locomotive activity. Inhibiting the function of synaptosomal-associated protein 25, a key SNARE protein involved in NMDAR exocytosis, blocked the increase of NMDAR-mediated EPSCs by low-dose MPH. In animals exposed to repeated stress, administration of low-dose MPH effectively restored NMDAR function and temporal order recognition memory via a mechanism dependent on synaptosomal-associated protein 25.
conclusionsThese results provide a potential mechanism underlying the cognitive-enhancing effects of low-dose MPH as well as the psychosis-inducing effects of high-dose MPH.
Indexed as
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What OpenQuestion holds
Registered trials
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.