ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine.
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. It is linked to trial NCT03781115 (Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia), which is not on this map. Cited by 24 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia
Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Haloperidol - norepinephrine synergy in stimulation of vacuous chewing movements in rats: Enhancement by nicotine.Psychopharmacology · 2026Article
- Clozapine impaired glucose-stimulated insulin secretion partly by increasing plasma 5-HT levels due to the inhibition of OCT1-mediated hepatic 5-HT uptake in mice.Acta pharmacologica Sinica · 2025Article
- Chemogenetics drives paradigm change in the investigation of behavioral circuits and neural mechanisms underlying drug action.Behavioural brain research · 2021Review
- Peripheral Blood Leukocyte RNA-Seq Identifies a Set of Genes Related to Abnormal Psychomotor Behavior Characteristics in Patients with Schizophrenia.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Influence of Schizophrenia-Associated Gene Egr3 on Sleep Behavior and Circadian Rhythms in Mice.Journal of biological rhythms · 2018Article
- Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia.Frontiers in behavioral neuroscience · 2018Article
- State-Dependent Modulation of Visual Evoked Potentials in a Rodent Genetic Model of Electroencephalographic Instability.Frontiers in systems neuroscience · 2018Article
- The Immediate Early GeneFrontiers in behavioral neuroscience · 2018Article
- Article
- Antipsychotic-induced Hdac2 transcription via NF-κB leads to synaptic and cognitive side effects.Nature neuroscience · 2017Article
- Precision medicine for suicidality: from universality to subtypes and personalization.Molecular psychiatry · 2017Article
- Reward Network Immediate Early Gene Expression in Mood Disorders.Frontiers in behavioral neuroscience · 2017Review
- Article
- Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3.Translational psychiatry · 2016Article
- Genomic structure and expression of the human serotonin 2A receptor gene (HTR2A) locus: identification of novel HTR2A and antisense (HTR2A-AS1) exons.BMC genetics · 2016Article
- Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3 receptors and BDNF in place preference acquisition.British journal of pharmacology · 2015Article
- Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent Manner.ACS chemical neuroscience · 2015Article
- Clozapine acts as an agonist at serotonin 2A receptors to counter MK-801-induced behaviors through a βarrestin2-independent activation of Akt.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5-HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for psychoses.The Journal of pharmacology and experimental therapeutics · 2014Article
- Locomotor hyperactivity in 14-3-3ζ KO mice is associated with dopamine transporter dysfunction.Translational psychiatry · 2013Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The immediate-early gene early growth response 3 (Egr3) is associated with schizophrenia and expressed at reduced levels in postmortem patients' brains. We have previously reported that Egr3-deficient (Egr3(-/-)) mice display reduced sensitivity to the sedating effects of clozapine compared with wild-type (WT) littermates, paralleling the heightened tolerance of schizophrenia patients to antipsychotic side effects. In this study, we have used a pharmacological dissection approach to identify a neurotransmitter receptor defect in Egr3(-/-) mice that may mediate their resistance to the locomotor suppressive effects of clozapine. We report that this response is specific to second-generation antipsychotic agents (SGAs), as first-generation medications suppress the locomotor activity of Egr3(-/-) and WT mice to a similar degree. Further, in contrast to the leading theory that sedation by clozapine results from anti-histaminergic effects, we show that H1 histamine receptors are not responsible for this effect in C57BL/6 mice. Instead, selective serotonin 2A receptor (5HT(2A)R) antagonists ketanserin and MDL-11939 replicate the effect of SGAs, repressing the activity in WT mice at a dosage that fails to suppress the activity of Egr3(-/-) mice. Radioligand binding revealed nearly 70% reduction in 5HT(2A)R expression in the prefrontal cortex of Egr3(-/-) mice compared with controls. Egr3(-/-) mice also exhibit a decreased head-twitch response to 5HT(2A)R agonist 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane (DOI). These findings provide a mechanism to explain the reduced sensitivity of Egr3(-/-) mice to the locomotor suppressive effects of SGAs, and suggest that 5HT(2A)Rs may also contribute to the sedating properties of these medications in humans. Moreover, as the deficit in cortical 5HT(2A)R in Egr3(-/-) mice aligns with numerous studies reporting decreased 5HT(2A)R levels in the brains of schizophrenia patients, and the gene encoding the 5HT(2A)R is itself a leading schizophrenia candidate gene, these findings suggest a potential mechanism by which putative dysfunction in EGR3 in humans may influence risk for schizophrenia.
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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.