ArticleBehavioural brain research2012
Genetic ablation of the GluK4 kainate receptor subunit causes anxiolytic and antidepressant-like behavior in mice.
Article in Behavioural brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.Molecular psychiatry · 2025Pooled it
- Design and Evaluation of Selective Positive Allosteric Modulators Targeting Kainate Receptors.ACS omega · 2026Article
- Structural insights into kainate receptor desensitization.Nature communications · 2025Article
- Theobromine prevents affective symptoms of nicotine withdrawal by modulating the neuroendocrine and immune systems, as well as the glutathione mechanism in the hippocampus.IBRO neuroscience reports · 2025Article
- Central role of regular firing neurons of centrolateral amygdala in affective behaviors.iScience · 2025Article
- Article
- Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel.Cell reports · 2023Article
- Habenula as a Possible Target for Treatment-Resistant Depression Phenotype in Wistar Kyoto Rats.Molecular neurobiology · 2023Article
- Biomarkers in Psychiatric Drug Development: From Precision Medicine to Novel Therapeutics.Advances in neurobiology · 2023Article
- Kainate receptors regulate the functional properties of young adult-born dentate granule cells.Cell reports · 2021Article
- Article
- Animal Models of Depression: What Can They Teach Us about the Human Disease?Diagnostics (Basel, Switzerland) · 2021Review
- Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update.Current neuropharmacology · 2021Review
- Intracellular Signaling Cascades in Bipolar Disorder.Current topics in behavioral neurosciences · 2021Review
- Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes.Neural plasticity · 2020Review
- Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities.Scientific reports · 2019Article
- Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Neurobiological Mechanisms of Stress Resilience and Implications for the Aged Population.Current neuropharmacology · 2018Review
- Cortical kainate receptors and behavioral anxiety.Molecular brain · 2017Review
- Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and Therapeutics of Mood Disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
There is a clear link between dysregulation of glutamatergic signaling and mood disorders. Genetic variants in the glutamate receptor gene GRIK4, which encodes the kainate receptor subunit GluK4, alter the susceptibility for depression, bipolar disorder and schizophrenia. Here we demonstrate that Grik4(-/-) mice have reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, Grik4(-/-) mice spent significantly more time exploring the open areas of the maze. In anxiogenic tests of marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim test, a test of learned helplessness that is used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting that Grik4 ablation has an antidepressant-like effect. Finally, in the sucrose preference test, a test for anhedonia in rodents, Grik4(-/-) mice demonstrated increased sucrose preference. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs are known to modulate synaptic plasticity. We tested whether Grik4 ablation had effects on mossy fiber (MF) plasticity and found there to be a significant impairment in LTP likely through a loss of KAR modulation of excitability of the presynaptic MF axons. These studies demonstrate a clear anxiolytic and antidepressant phenotype associated with ablation of Grik4 and a parallel disruption in hippocampal plasticity, providing support for the importance of this receptor subunit in mood disorders.
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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.