ArticleThe international journal of neuropsychopharmacology2012
Acute D-serine treatment produces antidepressant-like effects in rodents.
Article in The international journal of neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Bibliometric insights into astrocytic roles in depression and treatment.Frontiers in cellular neuroscience · 2024Pooled it
- Non-classical NMDAR subunit GluN3A in a specialized hippocampal region regulates stress-coping strategies in male mice.Communications biology · 2026Article
- Sex-related neuropsychiatric recovery from maternal perinatal depression and expression of monoamine and amino acid neurotransmitter levels in specific brain regions of adult offspring.Scientific reports · 2026Article
- Molecular Characterization of the Progressive Landscape of Depression.bioRxiv : the preprint server for biology · 2026Article
- GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy.Molecular psychiatry · 2026Article
- The Physicochemical, Nutritional, and Antioxidative Properties of Plant-Based Quinoa Yogurt.Food science & nutrition · 2025Article
- Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration.Translational psychiatry · 2025Article
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.Molecular psychiatry · 2024Article
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- The role of gut microbiota in the pathogenesis and treatment of postpartum depression.Annals of general psychiatry · 2023Review
- Astroglial Connexins Inactivation Increases Relapse of Depressive-like Phenotype after Antidepressant Withdrawal.International journal of molecular sciences · 2022Article
- D-Serine produces antidepressant-like effects in mice through suppression of BDNF signaling pathway and regulation of synaptic adaptations in the nucleus accumbens.Molecular medicine (Cambridge, Mass.) · 2021Article
- Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- D-Serine: A Cross Species Review of Safety.Frontiers in psychiatry · 2021Review
- Bacterial Metabolites of Human Gut Microbiota Correlating with Depression.International journal of molecular sciences · 2020Review
- D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders.Translational psychiatry · 2020Review
- Conformational flexibility within the small domain of human serine racemase.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers.Therapeutic advances in psychopharmacology · 2020Article
- Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function.Molecular psychiatry · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Research suggests that dysfunctional glutamatergic signalling may contribute to depression, a debilitating mood disorder affecting millions of individuals worldwide. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in approximately 70% of patients. Glutamate evokes the release of D-serine from astrocytes and neurons, which then acts as a co-agonist and binds at the glycine site on the NR1 subunit of NMDA receptors. Several studies have implicated glial deficits as one of the underlying facets of the neurobiology of depression. The present study tested the hypothesis that D-serine modulates behaviours related to depression. The behavioural effects of a single, acute D-serine administration were examined in several rodent tests of antidepressant-like effects, including the forced swim test (FST), the female urine sniffing test (FUST) following serotonin depletion, and the learned helplessness (LH) paradigm. D-serine significantly reduced immobility in the FST without affecting general motor function. Both D-serine and ketamine significantly rescued sexual reward-seeking deficits caused by serotonin depletion in the FUST. Finally, D-serine reversed LH behaviour, as measured by escape latency, number of escapes, and percentage of mice developing LH. Mice lacking NR1 expression in forebrain excitatory neurons exhibited a depression-like phenotype in the same behavioural tests, and did not respond to D-serine treatment. These findings suggest that D-serine produces antidepressant-like effects and support the notion of complex glutamatergic dysfunction in depression. It is unclear whether D-serine has a convergent influence on downstream synaptic plasticity cascades that may yield a similar therapeutic profile to NMDA antagonists like ketamine.
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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.