ArticleACS chemical neuroscience2010
Antipsychotic drugs activate the C. elegans akt pathway via the DAF-2 insulin/IGF-1 receptor.
Article in ACS chemical neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Suicide risk genes impact evolutionarily conserved survival strategies.Translational psychiatry · 2026Article
- Suicide risk genes impact evolutionarily conserved survival strategies.Research square · 2025Article
- Converging evidence for functional connections between the lithium response and PI3K-Akt signaling.Translational psychiatry · 2024Article
- Investigating the effects of antipsychotic drugs as a treatment for improving the activity of themicroPublication biology · 2024Article
- Evolutionary conservation of putative suicidality-related risk genes that produce diminished motivation corrected by clozapine, lithium and antidepressants.Frontiers in psychiatry · 2024Article
- Article
- Quetiapine Shortens the Lifespan ofInternational journal of molecular sciences · 2022Article
- Dopamine D1- and D2-like receptors oppositely regulate lifespan via a dietary restriction mechanism in Caenorhabditis elegans.BMC biology · 2022Article
- Elucidating the Possible Role of FoxO in Depression.Neurochemical research · 2021Review
- Hippocampal subfield transcriptome analysis in schizophrenia psychosis.Molecular psychiatry · 2021Article
- Schizophrenia and Epigenetic Aging Biomarkers: Increased Mortality, Reduced Cancer Risk, and Unique Clozapine Effects.Biological psychiatry · 2020Article
- Pharming for Genes in Neurotransmission: Combining Chemical and Genetic Approaches in Caenorhabditis elegans.ACS chemical neuroscience · 2018Review
- Crossing the Worm-Brain Barrier by UsingMolecular neuropsychiatry · 2018Review
- Caffeine Protects Dopaminergic Neurons From Dopamine-Induced Neurodegeneration via Synergistic Adenosine-Dopamine D2-Like Receptor Interactions in TransgenicFrontiers in neuroscience · 2018Article
- Insulin Signaling Deficiency Produces Immobility inMolecular neuropsychiatry · 2017Article
- The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway.Molecular neurobiology · 2017Article
- Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways.International journal of molecular sciences · 2014Review
- Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs.Frontiers in pharmacology · 2014Review
- A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target.PLoS genetics · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular modes of action of antipsychotic drugs are poorly understood beyond their effects at the dopamine D2 receptor. Previous studies have placed Akt signaling downstream of D2 dopamine receptors, and recent data have suggested an association between psychotic illnesses and defective Akt signaling. To characterize the effect of antipsychotic drugs on the Akt pathway, we used the model organism C. elegans, a simple system where the Akt/forkhead box O transcription factor (FOXO) pathway has been well characterized. All major classes of antipsychotic drugs increased signaling through the insulin/Akt/FOXO pathway, whereas four other drugs that are known to affect the central nervous system did not. The antipsychotic drugs inhibited dauer formation, dauer recovery, and shortened lifespan, three biological processes affected by Akt signaling. Genetic analysis showed that AKT-1 and the insulin and insulin-like growth factor receptor, DAF-2, were required for the antipsychotic drugs to increase signaling. Serotonin synthesis was partially involved, whereas the mitogen activated protein kinase (MAPK), SEK-1 is a MAP kinase kinase (MAPKK), and calcineurin were not involved. This is the first example of a common but specific molecular effect produced by all presently known antipsychotic drugs in any biological system. Because untreated schizophrenics have been reported to have low levels of Akt signaling, increased Akt signaling might contribute to the therapeutic actions of antipsychotic drugs.
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