ArticleThe European journal of neuroscience2016
Searching for cognitive enhancement in the Morris water maze: better and worse performance in D-amino acid oxidase knockout (Dao(-/-)) mice.
Article in The European journal of neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Human perceptual learning is delayed by the N-methyl-D-aspartate receptor partial agonist D-cycloserine.Journal of psychopharmacology (Oxford, England) · 2021Trial
- Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function.Molecular psychiatry · 2025Article
- Hippocampal Synaptic Plasticity: Integrating Memory and Anxiety Impairments in the Early Stages of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Behavioral Analysis of NMDAR Function in Rodents: Tests of Long-Term Spatial Memory.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Optimizing Choice and Timing of Behavioral Outcome Tests After Repetitive Mild Traumatic Brain Injury: A Machine Learning-Based Approach on Multiple Pre-Clinical Experiments.Journal of neurotrauma · 2023Article
- Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice.Cell reports · 2022Article
- Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice.International journal of molecular sciences · 2022Article
- Improvement of cognitive deficit of curcumin on scopolamine-induced Alzheimer's disease models.Caspian journal of internal medicine · 2022Article
- NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities.International journal of molecular sciences · 2021Review
- Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity.Molecular brain · 2021Article
- Emergence of synaptic and cognitive impairment in a mature-onset APP mouse model of Alzheimer's disease.Acta neuropathologica communications · 2019Article
- Can N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Be Localized to an Individual Cell Type?Frontiers in psychiatry · 2019Review
- Positive effects of systemic sodium benzoate and olanzapine treatment on activities of daily life, spatial learning and working memory in ketamine-induced rat model of schizophrenia.International journal of physiology, pathophysiology and pharmacology · 2019Article
- Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a.Nature communications · 2018Article
- Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2018Article
- Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.British journal of pharmacology · 2017Review
- Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
A common strategy when searching for cognitive-enhancing drugs has been to target the N-methyl-d-aspartate receptor (NMDAR), given its putative role in synaptic plasticity and learning. Evidence in favour of this approach has come primarily from studies with rodents using behavioural assays like the Morris water maze. D-amino acid oxidase (DAO) degrades neutral D-amino acids such as D-serine, the primary endogenous co-agonist acting at the glycine site of the synaptic NMDAR. Inhibiting DAO could therefore provide an effective and viable means of enhancing cognition, particularly in disorders like schizophrenia, in which NMDAR hypofunction is implicated. Indirect support for this notion comes from the enhanced hippocampal long-term potentiation and facilitated water maze acquisition of ddY/Dao(-) mice, which lack DAO activity due to a point mutation in the gene. Here, in Dao knockout (Dao(-/-) ) mice, we report both better and worse water maze performance, depending on the radial distance of the hidden platform from the side wall of the pool. Dao(-/-) mice displayed an increased innate preference for swimming in the periphery of the maze (possibly due to heightened anxiety), which facilitated the discovery of a peripherally located platform, but delayed the discovery of a centrally located platform. By contrast, Dao(-/-) mice exhibited normal performance in two alternative assays of long-term spatial memory: the appetitive and aversive Y-maze reference memory tasks. Taken together, these results question the proposed relationship between DAO inactivation and enhanced long-term associative spatial memory. They also have generic implications for how Morris water maze studies are performed and interpreted.
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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.