ArticleFrontiers in pharmacology2018
Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Repurposing Caffeine, Metformin, and Furosemide to Target Schizophrenia-Related Impairments in a Triple-Hit Rat Model.International journal of molecular sciences · 2025Article
- Behavioral characterization of triple-hit schizophrenia-like Lisket rats derived from the Long Evans strain through acute and chronic behavioral tests.Frontiers in psychiatry · 2025Article
- Behavioral and transcriptional effects of repeated electroconvulsive seizures in the neonatal MK-801-treated rat model of schizophrenia.Psychopharmacology · 2024Article
- MK-801 and cognitive functions: Investigating the behavioral effects of a non-competitive NMDA receptor antagonist.Psychopharmacology · 2023Review
- Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box-Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route.Pharmaceutics · 2023Article
- Repeated dextromethorphan administration in adolescent rats produces long-lasting behavioral alterations.Pharmacology, biochemistry, and behavior · 2023Article
- Receptor-Mediated AKT/PI3K Signalling and Behavioural Alterations in Zebrafish Larvae Reveal Association between Schizophrenia and Opioid Use Disorder.International journal of molecular sciences · 2022Article
- Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis.Behavioral and brain functions : BBF · 2021Review
- Article
- Behavioral Consequences of a Combination ofFrontiers in pharmacology · 2021Article
- CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration.Frontiers in pharmacology · 2021Article
- Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes.Frontiers in cell and developmental biology · 2020Article
- Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?Frontiers in pharmacology · 2020Review
- Enriched environment improves sevoflurane-induced cognitive impairment during late-pregnancy via hippocampal histone acetylation.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus.Frontiers in neuroscience · 2020Article
- Long-lasting effects of repeated ketamine administration in adult and adolescent rats.Behavioural brain research · 2019Article
- Reversal of MK-801-Induced Disruptions in Social Interactions and Working Memory with Simultaneous Administration of LY487379 and VU152100 in Mice.International journal of molecular sciences · 2019Article
- Vinpocetine halts ketamine-induced schizophrenia-like deficits in rats: impact on BDNF and GSK-3β/β-catenin pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of NMDA receptors in learning, memory and hippocampal function has long been recognized. Post-mortem studies have indicated that the expression or subunit composition of the NMDA glutamate receptor subtype might be related to the impaired cognitive functions found in schizophrenia patients. NMDA receptor antagonists have been used to develop animal models of this disorder. There is accumulating evidence showing that not only the acute but also the chronic application of NMDA receptor antagonists may induce schizophrenia-like alterations in behavior and brain functions. However, limited evidence is available regarding the consequences of NMDA receptor blockage during periods of adolescence and early adulthood. This study tested the hypothesis that a 2-week treatment of male Long-Evans and Wistar rats with dizocilpine (MK-801; 0.5 mg/kg daily) starting at postnatal days (PD) 30 and 60 would cause a long-term cognitive deficit and changes in the levels of NMDA receptor subunits. The working memory version of the Morris water maze (MWM) and active place avoidance with reversal on a rotating arena (Carousel) requiring cognitive coordination and flexibility probed cognitive functions and an elevated-plus maze (EPM) was used to measure anxiety-like behavior. The western blot method was used to determine changes in NMDA receptor subunit levels in the hippocampus. Our results showed no significant changes in behaviors in Wistar rats. Slightly elevated anxiety-like behavior was observed in the EPM in Long-Evans rats with the onset of treatment on PD 30. Furthermore, Long-Evans rats treated from PD 60 displayed impaired working memory in the MWM. There were; however, no significant changes in the levels of NMDA receptor subunits because of MK-801 administration. These findings suggest that a 2-week treatment starting on PD 60 in Long-Evans rats leads to long-term changes in working memory, but this deficit is not paralleled by changes in NMDA receptor subunits. These results support the face validity, but not construct validity of this model. We suggest that chronic treatment of adolescent and adult rats does not constitute a plausible animal model of schizophrenia.
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