ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Environmental Enrichment Ameliorates Behavioral Impairments Modeling Schizophrenia in Mice Lacking Metabotropic Glutamate Receptor 5.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Molecular insights into enriched environments and behavioral improvements in autism: a systematic review and meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sex-dependent Schizophrenia and Drug Reward Behavioral Phenotypes in Metabotropic Glutamate 5 Receptor Heterozygous and Homozygous Mice.Schizophrenia bulletin · 2026Article
- Prebiotics Rescue Gut Microbiome Dysregulation and Enhance Cognitive and Gastrointestinal Function in a Mouse Model of Schizophrenia.Schizophrenia bulletin · 2026Article
- GABAFrontiers in pharmacology · 2026Review
- Conspecific Presence Promotes Social Buffering, Restores Social Reward, and Enhances Spatial Navigation in a Ketamine-Induced Model of Schizophrenia in Mice.The European journal of neuroscience · 2025Article
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Postnatal environment affects auditory development and sensorimotor gating in a rat model for autism spectrum disorder.Frontiers in neuroscience · 2025Article
- Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson's disease.Neural regeneration research · 2023Review
- Neurobehavioral effects of environmental enrichment and drug abuse vulnerability: An updated review.Pharmacology, biochemistry, and behavior · 2022Review
- Metabotropic Glutamate Receptors As Emerging Targets for the Treatment of Schizophrenia.Molecular pharmacology · 2022Review
- Use of prepubertal environment enrichment to prevent dopamine dysregulation in a neurodevelopmental rat model of schizophrenia risk.STAR protocols · 2022Article
- The effects and mechanism of environmental enrichment on MK-801 induced cognitive impairment in rodents with schizophrenia.Frontiers in cellular neuroscience · 2022Review
- Timely N-Acetyl-Cysteine and Environmental Enrichment Rescue Oxidative Stress-Induced Parvalbumin Interneuron Impairments via MMP9/RAGE Pathway: A Translational Approach for Early Intervention in Psychosis.Schizophrenia bulletin · 2021Article
- Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities inGenes · 2021Article
- Environmental enrichment or selective activation of parvalbumin-expressing interneurons ameliorates synaptic and behavioral deficits in animal models with schizophrenia-like behaviors during adolescence.Molecular psychiatry · 2021Article
- Prepubertal Environmental Enrichment Prevents Dopamine Dysregulation and Hippocampal Hyperactivity in MAM Schizophrenia Model Rats.Biological psychiatry · 2021Article
- Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update.Current neuropharmacology · 2021Review
- Microbiome Profiling Reveals Gut Dysbiosis in the Metabotropic Glutamate Receptor 5 Knockout Mouse Model of Schizophrenia.Frontiers in cell and developmental biology · 2020Article
- Duration of Environmental Enrichment Determines Astrocyte Number and Cervical Lymph Node T Lymphocyte Proportions but Not the Microglial Number in Middle-Aged C57BL/6 Mice.Frontiers in cellular neuroscience · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia arises from a complex interplay between genetic and environmental factors. Abnormalities in glutamatergic signaling have been proposed to underlie the emergence of symptoms, in light of various lines of evidence, including the psychotomimetic effects of NMDA receptor antagonists. Metabotropic glutamate receptor 5 (mGlu5) has also been implicated in the disorder, and has been shown to physically interact with NMDA receptors. To clarify the role of mGlu5-dependent behavioral expression by environmental factors, we assessed mGlu5 knockout (KO) mice after exposure to environmental enrichment (EE) or reared under standard conditions. The mGlu5 KO mice showed reduced prepulse inhibition (PPI), long-term memory deficits, and spontaneous locomotor hyperactivity, which were all attenuated by EE. Examining the cellular impact of genetic and environmental manipulation, we show that EE significantly increased pyramidal cell dendritic branching and BDNF protein levels in the hippocampus of wild-type mice; however, mGlu5 KO mice were resistant to these alterations, suggesting that mGlu5 is critical to these responses. A selective effect of EE on the behavioral response to the NMDA receptor antagonist MK-801 in mGlu5 KO mice was seen. MK-801-induced hyperlocomotion was further potentiated in enriched mGlu5 KO mice and treatment with MK-801 reinstated PPI disruption in EE mGlu5 KO mice only, a response that is absent under standard housing conditions. Together, these results demonstrate an important role for mGlu5 in environmental modulation of schizophrenia-related behavioral impairments. Furthermore, this role of the mGlu5 receptor is mediated by interaction with NMDA receptor function, which may inform development of novel therapeutics.
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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.