ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Selective remediation of reversal learning deficits in the neurodevelopmental MAM model of schizophrenia by a novel mGlu5 positive allosteric modulator.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- Prefrontal and Hippocampal Parvalbumin Interneurons in Animal Models for Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2024Pooled it
- Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2019Trial
- Valence-Driven Cognitive Flexibility: Neurochemical and Circuit-Level Insights from Animal Models and Their Relevance to Schizophrenia.Biomolecules · 2025Review
- Infant rat ultrasonic vocalizations in the neurodevelopmental model of schizophrenia.Scientific reports · 2025Article
- Computational modeling of reversal learning impairments in schizophrenia and bipolar disorder reveals shared failure to exploit rewards.Journal of psychopathology and clinical science · 2025Article
- mGluR5 positive allosteric modulation prevents MK-801 induced increases in extracellular glutamate in the rat medial prefrontal cortex.Neuroscience · 2024Article
- Visual cortex repetitive transcranial magnetic stimulation (rTMS) reversing neurodevelopmental impairments in adolescents with major psychiatric disorders (MPDs): A cross-species translational study.CNS neuroscience & therapeutics · 2024Article
- Developmental Manipulation-Induced Changes in Cognitive Functioning.Current topics in behavioral neurosciences · 2023Article
- Metabotropic Glutamate Receptors As Emerging Targets for the Treatment of Schizophrenia.Molecular pharmacology · 2022Review
- Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia.Biomolecules · 2022Article
- The Antioxidant N-Acetyl-L-Cysteine Restores the Behavioral Deficits in a Neurodevelopmental Model of Schizophrenia Through a Mechanism That Involves Nitric Oxide.Frontiers in pharmacology · 2022Article
- Peripubertal mGluR2/3 Agonist Treatment Prevents Hippocampal Dysfunction and Dopamine System Hyperactivity in Adulthood in MAM Model of Schizophrenia.Schizophrenia bulletin · 2021Article
- Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia.Translational psychiatry · 2021Article
- Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology.Psychopharmacology · 2021Review
- Translation-Focused Approaches to GPCR Drug Discovery for Cognitive Impairments Associated with Schizophrenia.ACS pharmacology & translational science · 2020Review
- Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Article
- Insights on current and novel antipsychotic mechanisms from the MAM model of schizophrenia.Neuropharmacology · 2020Review
- Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.Frontiers in pharmacology · 2020Review
- Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model.Current Alzheimer research · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Based on the glutamatergic hypothesis of schizophrenia we assessed the effects of a novel mGlu5 positive allosteric modulator, LSN2463359 [N-(1-methylethyl)-5-(pyridin-4-ylethynyl)pyridine-2-carboxamide] on deficits in cognitive flexibility in two distinct rodent models of schizophrenia, the neurodevelopmental MAM E17 model and the acute PCP model. Cognitive flexibility was measured with the intra-dimensional and extra-dimensional set-shifting and reversal learning digging paradigm. Regional effects of MAM on the expression of parvalbumin-positive cells (PV) and mGlu5 receptors were also examined, to further characterize the model. Results showed that LSN2463359 selectively attenuated reversal learning deficits in the MAM but not acute PCP model. Whilst both models led to deficits in reversal learning and extra-dimensional set-shifting, the reversal impairments were qualitatively distinct, with MAM increasing perseverative responding, whereas the PCP deficit was mainly due to the inability of rats to maintain reinforced choice behavior. Reduction of PV and mGlu5 expression was found in the MAM model in several regions of importance in schizophrenia, such as the orbitofrontal and medial prefrontal cortex, which also mediate reversal learning and extra-dimensional set-shifting. The present findings confirm that the positive modulation of mGlu5 receptors may have beneficial effects in the treatment of certain aspects of cognitive impairment associated with schizophrenia. This study also illustrates the importance of studying putative cognitive enhancing drug effects in a number of models which may have implications for the future development of the compound.
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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.