ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
The role of GluN2A and GluN2B subunits on the effects of NMDA receptor antagonists in modeling schizophrenia and treating refractory depression.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 76 citations in OpenAlex.
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- Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes.Current neuropharmacology · 2026Review
- Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.Synapse (New York, N.Y.) · 2025Article
- Regulation of Cerebral BDNF, VEGF, and GluN2B Gene Expression and Cytokine Levels by Riparin A in a Murine Model of Depression.Advances in pharmacological and pharmaceutical sciences · 2025Article
- High and Low Dose Ketamine in Post-Traumatic Stress Disorder.Anesthesia and critical care (Houston, Tex.) · 2025Article
- GluN2A: A Promising Target for Developing Novel Antidepressants.The international journal of neuropsychopharmacology · 2024Review
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- GluN2B subunit selective N-methyl-D-aspartate receptor ligands: Democratizing recent progress to assist the development of novel neurotherapeutics.Molecular diversity · 2024Review
- GluN2A mediates ketamine-induced rapid antidepressant-like responses.Nature neuroscience · 2023Article
- Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators.Cellular and molecular neurobiology · 2023Review
- The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia.Nutrients · 2022Review
- Effects of NMDA receptor antagonists on behavioral economic indices of cocaine self-administration.Drug and alcohol dependence · 2022Article
- Alteration in NMDAR subunits in different brain regions of chronic unpredictable mild stress (CUMS) rat model.Translational neuroscience · 2022Article
- Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study.Brain structure & function · 2021Article
- Effects of the GluN2B-selective antagonist Ro 63-1908 on acquisition and expression of methamphetamine conditioned place preference in male and female rats.Drug and alcohol dependence · 2021Article
- Advances in novel molecular targets for antidepressants.Progress in neuro-psychopharmacology & biological psychiatry · 2021Review
- Differential effects of glutamate N-methyl-D-aspartate receptor antagonists on risky choice as assessed in the risky decision task.Psychopharmacology · 2021Article
- Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions.International journal of molecular sciences · 2020Review
- Brain NMDA Receptors in Schizophrenia and Depression.Biomolecules · 2020Review
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression.Molecular brain · 2020Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paradoxically, N-methyl-D-aspartate (NMDA) receptor antagonists are used to model certain aspects of schizophrenia as well as to treat refractory depression. However, the role of different subunits of the NMDA receptor in both conditions is poorly understood. Here we used biochemical and behavioral readouts to examine the in vivo prefrontal efflux of serotonin and glutamate as well as the stereotypical behavior and the antidepressant-like activity in the forced swim test elicited by antagonists selective for the GluN2A (NVP-AAM077) and GluN2B (Ro 25-6981) subunits. The effects of the non-subunit selective antagonist, MK-801; were also studied for comparison. The administration of MK-801 dose dependently increased the prefrontal efflux of serotonin and glutamate and markedly increased the stereotypy scores. NVP-AAM077 also increased the efflux of serotonin and glutamate, but without the induction of stereotypies. In contrast, Ro 25-6981 did not change any of the biochemical and behavioral parameters tested. Interestingly, the administration of NVP-AAM077 and Ro 25-6981 alone elicited antidepressant-like activity in the forced swim test, in contrast to the combination of both compounds that evoked marked stereotypies. Our interpretation of the results is that both GluN2A and GluN2B subunits are needed to induce stereotypies, which might be suggestive of potential psychotomimetic effects in humans, but the antagonism of only one of these subunits is sufficient to evoke an antidepressant response. We also propose that GluN2A receptor antagonists could have potential antidepressant activity in the absence of potential psychotomimetic effects.
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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.