ArticleScience signaling2014
Antipsychotics activate mTORC1-dependent translation to enhance neuronal morphological complexity.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 63 citations in OpenAlex.
- Neurostimulation in the treatment of psychiatric disorders: Underlying mechanisms and critical analysis of circuit-based interventions.Molecular psychiatry · 2026Review
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Structural neural plasticity evoked by rapid-acting antidepressant interventions.Nature reviews. Neuroscience · 2025Review
- Boolean Modeling of Biological Network Applied to Protein-Protein Interaction Network of Autism Patients.Biology · 2024Article
- Multigenerational, Indirect Exposure to Pyrethroids Demonstrates Potential Compensatory Response and Reduced Toxicity at Higher Salinity in Estuarine Fish.Environmental science & technology · 2024Article
- Cellular and molecular signatures of motherhood in the adult and ageing rat brain.Open biology · 2023Article
- GSK3β and mTORC1 Represent 2 Distinct Signaling Markers in Peripheral Blood Mononuclear Cells of Drug-Naive, First Episode of Psychosis Patients.Schizophrenia bulletin · 2022Article
- Molecular mechanisms of antipsychotics - their influence on intracellular signaling pathways, and epigenetic and post-transcription processes.Postepy psychiatrii neurologii · 2022Review
- Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.Translational psychiatry · 2022Review
- mTOR kinase activity disrupts a phosphorylation signaling network in schizophrenia brain.Molecular psychiatry · 2021Article
- Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine.Neurochemical research · 2021Article
- Age-dependent shift in the de novo proteome accompanies pathogenesis in an Alzheimer's disease mouse model.Communications biology · 2021Article
- Hippocampal subfield transcriptome analysis in schizophrenia psychosis.Molecular psychiatry · 2021Article
- Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia.International journal of molecular sciences · 2021Article
- Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells.International journal of molecular sciences · 2021Article
- The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior.Translational psychiatry · 2020Article
- Disregulation of Autophagy in the Transgenerational Cc2d1a Mouse Model of Autism.Neuromolecular medicine · 2020Article
- Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia.Frontiers in pharmacology · 2020Article
- Developmental exposure to environmentally relevant concentrations of bifenthrin alters transcription of mTOR and ryanodine receptor-dependent signaling molecules and impairs predator avoidance behavior across early life stages in inland silversides (Menidia beryllina).Aquatic toxicology (Amsterdam, Netherlands) · 2019Article
- Comparative psychopharmacology of autism and psychotic-affective disorders suggests new targets for treatment.Evolution, medicine, and public health · 2019Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Although antipsychotic drugs can reduce psychotic behavior within a few hours, full efficacy is not achieved for several weeks, implying that there may be rapid, short-term changes in neuronal function, which are consolidated into long-lasting changes. We showed that the antipsychotic drug haloperidol, a dopamine receptor type 2 (D₂R) antagonist, stimulated the kinase Akt to activate the mRNA translation pathway mediated by the mammalian target of rapamycin complex 1 (mTORC1). In primary striatal D₂R-positive neurons, haloperidol-mediated activation of mTORC1 resulted in increased phosphorylation of ribosomal protein S6 (S6) and eukaryotic translation initiation factor 4E-binding protein (4E-BP). Proteomic mass spectrometry revealed marked changes in the pattern of protein synthesis after acute exposure of cultured striatal neurons to haloperidol, including increased abundance of cytoskeletal proteins and proteins associated with translation machinery. These proteomic changes coincided with increased morphological complexity of neurons that was diminished by inhibition of downstream effectors of mTORC1, suggesting that mTORC1-dependent translation enhances neuronal complexity in response to haloperidol. In vivo, we observed rapid morphological changes with a concomitant increase in the abundance of cytoskeletal proteins in cortical neurons of haloperidol-injected mice. These results suggest a mechanism for both the acute and long-term actions of antipsychotics.
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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.