ArticleBrain research2011
Behavioral effects of clozapine: involvement of trace amine pathways in C. elegans and M. musculus.
Article in Brain research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Trace Amine-associated Receptors (TAARs): Candidate Targets in the Treatment of Bipolar Disorders.Actas espanolas de psiquiatria · 2025Review
- Peering into the mind: unraveling schizophrenia's secrets using models.Molecular psychiatry · 2025Review
- Unlocking the secrets of trace amine-associated receptor 1 agonists: new horizon in neuropsychiatric treatment.Frontiers in psychiatry · 2024Review
- Morphological and transcriptomic analyses of stem cell-derived cortical neurons reveal mechanisms underlying synaptic dysfunction in schizophrenia.Genome medicine · 2023Article
- Haloperidol Interactions with the dop-3 Receptor in Caenorhabditis elegans.Molecular neurobiology · 2021Article
- Advances toward precision medicine for bipolar disorder: mechanisms & molecules.Molecular psychiatry · 2021Review
- Trace Amine-Associated Receptor 1 Agonist Modulates Mismatch Negativity-Like Responses in Mice.Frontiers in pharmacology · 2019Article
- Crossing the Worm-Brain Barrier by UsingMolecular neuropsychiatry · 2018Review
- Clozapine Modulates Glucosylceramide, Clears Aggregated Proteins, and Enhances ATG8/LC3 in Caenorhabditis elegans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Methods for studying the mechanisms of action of antipsychotic drugs in Caenorhabditis elegans.Journal of visualized experiments : JoVE · 2014Article
- Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs.Frontiers in pharmacology · 2014Review
- A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight.Molecular psychiatry · 2013Article
- A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target.PLoS genetics · 2013Article
- Genetic models of sensorimotor gating: relevance to neuropsychiatric disorders.Current topics in behavioral neurosciences · 2012Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Clozapine is an antipsychotic medication with superior efficacy in treatment refractory schizophrenia. The molecular basis of clozapine's therapeutic profile is not well understood. We studied behavioral effects of clozapine in Caenorhabditis elegans to identify novel pathways that modulate clozapine's biological effects. Clozapine stimulated egg laying in C. elegans in a dose-dependent manner. This effect was clozapine-specific, as it was not observed with exposure to a typical antipsychotic, haloperidol or an atypical antipsychotic, olanzapine. A candidate gene screen of biogenic amine neurotransmitter systems identified signaling pathways that mediate this clozapine-specific effect on egg laying. Specifically, we found that clozapine-induced increase in egg laying requires tyramine biosynthesis. To test the implications of this finding across species, we explored whether trace amine systems modulate clozapine's behavioral effects in mammals by studying trace amine-associated receptor 1 (TAAR1) knockout mice. Clozapine increased prepulse inhibition (PPI) in wild-type mice. This increase in PPI was abrogated in TAAR1 knockout mice, implicating TAAR1 in clozapine-induced PPI enhancement. In transfected mammalian cell lines, we found no TAAR activation by antipsychotics, suggesting that modulation of trace amine signaling in mice does not occur directly at the receptor itself. In summary, we report a heretofore-unknown role for trace amine systems in clozapine-mediated effects across two species: C. elegans and mice.
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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.