ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Amphetamine improves mouse and human attention in the 5-choice continuous performance test.Neuropharmacology · 2018Trial
- Modafinil improves attentional performance in healthy, non-sleep deprived humans at doses not inducing hyperarousal across species.Neuropharmacology · 2017Trial
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- Cross-species translational paradigms for assessing positive valence system as defined by the RDoC matrix.Journal of neurochemistry · 2025Review
- Org24598, a Selective Glycine Transporter 1 (GlyT1) Inhibitor, Reverses Object Recognition and Spatial Memory Impairments Following Binge-like Ethanol Exposure in Rats.Molecules (Basel, Switzerland) · 2024Article
- Amphetamine increases motivation of humans and mice as measured by breakpoint, but does not affect an Electroencephalographic biomarker.Cognitive, affective & behavioral neuroscience · 2024Article
- Modulation of ventromedial orbitofrontal cortical glutamatergic activity affects the explore-exploit balance and influences value-based decision-making.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor.International journal of molecular sciences · 2022Article
- A low-cost open-source 5-choice operant box system optimized for electrophysiology and optophysiology in mice.Scientific reports · 2021Article
- Transcription Factor Motifs Associated with Anterior Insula Gene Expression Underlying Mood Disorder Phenotypes.Molecular neurobiology · 2021Article
- Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT.Bipolar disorders · 2020Article
- Oxytocin improves probabilistic reversal learning but not effortful motivation in Brown Norway rats.Neuropharmacology · 2019Article
- Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1.Translational psychiatry · 2019Article
- Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2018Article
- Reverse translated and gold standard continuous performance tests predict global cognitive performance in schizophrenia.Translational psychiatry · 2018Article
- The 5 choice continuous performance test (5C-CPT): A novel tool to assess cognitive control across species.Journal of neuroscience methods · 2017Review
- Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.British journal of pharmacology · 2017Review
- Preclinical Models to Investigate Mechanisms of Negative Symptoms in Schizophrenia.Schizophrenia bulletin · 2017Review
- Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice.Psychopharmacology · 2017Article
- Dysregulated Glycine Signaling Contributes to Increased Impulsivity during Protracted Alcohol Abstinence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Serious mental illness occurs in 25% of the general population, with many disorders being neurodevelopmental, lifelong, and debilitating. The wide variation and overlap in symptoms across disorders increases the difficulty of research and treatment development. The NIMH Research Domain of Criteria initiative aims to improve our understanding of the molecular and behavioral consequences of specific neurodevelopmental mechanisms across disorders, enabling targeted treatment development. The transcription factor Specificity Protein 4 (SP4) is important for neurodevelopment and is genetically associated with both schizophrenia and bipolar disorder. Reduced Sp4 expression in mice (hypomorphic) reproduces several characteristics of psychiatric disorders. We further tested the utility of Sp4 hypomorphic mice as a model organism relevant to psychiatric disorders by assessing cognitive control plus effort and decision-making aspects of approach motivation using cross-species-relevant tests. Sp4 hypomorphic mice exhibited impaired attention as measured by the 5-Choice Continuous Performance Test, an effect that was attenuated by glycine type-1 transporter (GlyT-1) inhibition. Hypomorphic mice also exhibited reduced motivation to work for a reward and impaired probabilistic learning. These deficits may stem from affected anticipatory reward, analogous to anhedonia in patients with schizophrenia and other psychiatric disorders. Neither positive valence deficit was attenuated by GlyT-1 treatment, suggesting that these and the attentional deficits stem from different underlying mechanisms. Given the association of SP4 gene with schizophrenia and bipolar disorder, the present studies provide support that personalized GlyT-1 inhibition may treat attentional deficits in neuropsychiatric patients with low SP4 levels.
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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.