ArticlePsychopharmacology2008
Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia.
Article in Psychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Relevance of diet in schizophrenia: a review focusing on prenatal nutritional deficiency, obesity, oxidative stress and inflammation.Frontiers in nutrition · 2024Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Negative symptom improvement during cognitive rehabilitation: results from a 2-year trial of Cognitive Enhancement Therapy.Psychiatry research · 2013Trial
- Oral glycine administration increases brain glycine/creatine ratios in men: a proton magnetic resonance spectroscopy study.Psychiatry research · 2009Trial
- A trial of D-cycloserine to treat stereotypies in older adolescents and young adults with autism spectrum disorder.Clinical neuropharmacologyTrial
- Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025Review
- Metabolomics, Lipidomics, and Antipsychotics: A Systematic Review.Biomedicines · 2023Review
- Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals.Biomedicines · 2023Article
- Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia.International journal of molecular sciences · 2023Review
- Synergistic, long-term effects of glutamate dehydrogenase 1 deficiency and mild stress on cognitive function and mPFC gene and miRNA expression.Translational psychiatry · 2023Article
- Article
- Histamine HProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species.Current topics in behavioral neurosciences · 2023Review
- Proteomic signatures of schizophrenia-sourced iPSC-derived neural cells and brain organoids are similar to patients' postmortem brains.Cell & bioscience · 2022Article
- Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs.Neuropharmacology · 2021Review
- Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia.Frontiers in psychiatry · 2021Review
- Putative modulation of the gut microbiome by probiotics enhances preference for novelty in a preliminary double-blind placebo-controlled study in ferrets.Animal microbiome · 2020Article
- The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents.International journal of molecular sciences · 2019Review
- Neuronal serine racemase associates with Disrupted-In-Schizophrenia-1 and DISC1 agglomerates: Implications for schizophrenia.Neuroscience letters · 2019Article
- NMDAR Hypofunction Animal Models of Schizophrenia.Frontiers in molecular neuroscience · 2019Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleSchizophrenic patients demonstrate prominent negative and cognitive symptoms that are poorly responsive to antipsychotic treatment. Abnormal glutamatergic neurotransmission may contribute to these pathophysiological dimensions of schizophrenia.
objectiveWe examined the involvement of the glycine coagonist site on the N-methyl-D: -aspartate receptor (NMDAR) glycine coagonist site in the modulation of negative and cognitive endophenotypes in mice. MATERIALS AND
methodsBehavioral phenotypes relevant to schizophrenia were assessed in Grin1(D481N) mice that have reduced NMDAR glycine affinity.
resultsGrin1(D481N) mutant mice showed abnormally persistent latent inhibition (LI) that was reversed by two agents that enhance NMDAR glycine site function, D: -serine (600 mg/kg) and ALX-5407 (1 mg/kg), and by the classical atypical antipsychotic clozapine (3 mg/kg). Similarly, blockade of the NMDAR glycine site with the antagonist L-701,324 (5 mg/kg) induced persistent LI in C57BL6/J mice. In a social affiliations task, Grin1(D481N) mutant animals showed reduced social approach behaviors that were normalized by D: -serine (600 mg/kg). During a nonassociative spatial object recognition task, mutant mice demonstrated impaired reactivity to a spatial change that was reversible by D: -serine (300 and 600 mg/kg) and clozapine (0.75 mg/kg). In contrast, responses to social novelty and nonspatial change remained unaffected, indicating that the Grin1(D481N) mutation induces selective deficits in sociability and spatial discrimination, while leaving intact the ability to react to novelty.
conclusionsGenetic and pharmacologically induced deficiencies in glycine binding appear to model the impairments in behavioral flexibility, sociability, and spatial recognition related to the negative and cognitive symptoms of schizophrenia. Antipsychotics that target the NMDAR glycine site may be beneficial in treating such psychiatric symptoms.
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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.