ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Neuropsychiatric Phenotypes Produced by GABA Reduction in Mouse Cortex and Hippocampus.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
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- The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events.Science advances · 2026Article
- Downregulation of AdipoR1 in the hippocampus impairs synaptic function and structure and causes depression-like behavior.Translational psychiatry · 2025Article
- Group 2 innate lymphoid cells drive inhibitory synapse formation with lasting effects on learning and memory.Journal of neuroinflammation · 2025Article
- Nurture outpaces nature: fostering with an attentive mother alters social dominance in a mouse model of stress sensitivity.Molecular psychiatry · 2023Article
- Behavioral State-Dependent Modulation of Prefrontal Cortex Activity by Respiration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
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- Motivational disturbances in rodent models of neuropsychiatric disorders.Frontiers in behavioral neuroscience · 2022Review
- Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications.Neuroscience bulletin · 2021Review
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- Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice.Molecular brain · 2021Article
- A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms.Frontiers in cell and developmental biology · 2021Review
- Glutamate and GABA Homeostasis and Neurometabolism in Major Depressive Disorder.Frontiers in psychiatry · 2021Review
- GABAergic System Dysfunction and Challenges in Schizophrenia Research.Frontiers in cell and developmental biology · 2021Review
- CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia.Translational psychiatry · 2020Article
- Disinhibition of somatostatin interneurons confers resilience to stress in male but not female mice.Neurobiology of stress · 2020Article
- Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems.Brain structure & function · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Whereas cortical GAD67 reduction and subsequent GABA level decrease are consistently observed in schizophrenia and depression, it remains unclear how these GABAergic abnormalities contribute to specific symptoms. We modeled cortical GAD67 reduction in mice, in which the Gad1 gene is genetically ablated from ~50% of cortical and hippocampal interneurons. Mutant mice showed a reduction of tissue GABA in the hippocampus and cortex including mPFC, and exhibited a cluster of effort-based behavior deficits including decreased home-cage wheel running and increased immobility in both tail suspension and forced swim tests. Since saccharine preference, progressive ratio responding to food, and learned helplessness task were normal, such avolition-like behavior could not be explained by anhedonia or behavioral despair. In line with the prevailing view that dopamine in anterior cingulate cortex (ACC) plays a role in evaluating effort cost for engaging in actions, we found that tail-suspension triggered dopamine release in ACC of controls, which was severely attenuated in the mutant mice. Conversely, ACC dopamine release by progressive ratio responding to reward, during which animals were allowed to effortlessly perform the nose-poking, was not affected in mutants. These results suggest that cortical GABA reduction preferentially impairs the effort-based behavior which requires much effort with little benefit, through a deficit of ACC dopamine release triggered by high-effort cost behavior, but not by reward-seeking behavior. Collectively, a subset of negative symptoms with a reduced willingness to expend costly effort, often observed in patients with schizophrenia and depression, may be attributed to cortical GABA level reduction.
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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.