ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Molecular Psychiatry
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1581524
Lurasidone Induces Developmental Toxicity and Behavioral Impairments in Zebrafish Embryos
Provisionally accepted
- 1Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, Shanghai Municipality, China
- 2Wuhan Mental Health Center, Wuhan, Hubei Province, China
- 3Hubei Normal University, Huangshi, China
- 4Department of Physics, School of Mathematics and Science, China University of Geosciences Wuhan, Wuhan, Hubei Province, China
- 5Wuhan Medical Center for Women and Children, Wuhan, Hubei Province, China
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Lurasidone, a second-generation antipsychotic, is widely used for treating schizophrenia and bipolar disorder due to its favorable metabolic profile. However, its potential developmental neurotoxicity remains poorly understood. This study investigated the effects of lurasidone on zebrafish embryos, combining morphological, behavioral, transcriptomic, and neurotransmitter analyses. Zebrafish embryos were exposed to lurasidone at 0, 0.4, 4, and 8 mg/L concentrations from 5 to 120 hours post-fertilization (hpf). Results revealed dose-dependent developmental toxicity, including reduced survival and hatching rates, shorter body length, and increased pericardial and yolk sac edema. Behavioral assessments showed significant impairments in locomotion and touch response, particularly at higher concentrations. Transcriptomic analysis identified 1,907 differentially expressed genes, with upregulation of circadian regulation pathways and downregulation of cell cycle and oxidative phosphorylation pathways.Neurotransmitter profiling indicated significant reductions in glutamate, dopamine, and GABA levels, suggesting disruptions in excitatory/inhibitory balance. These findings highlight lurasidone's potential neurodevelopmental risks, particularly during critical developmental periods. The study underscores the importance of further research to assess the safety of lurasidone in vulnerable populations, such as pregnant women and young patients.
Keywords: lurasidone, Neurotoxicity, Zebrafish embryo model, Neurotransmitter Systems, behavioral toxicology
Received: 11 Mar 2025; Accepted: 23 May 2025.
Copyright: © 2025 Li, Wang, Feng, Cheng, Huang, Zhu, Xiao and Hongjian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Han Xiao, Wuhan Medical Center for Women and Children, Wuhan, Hubei Province, China
Gong Hongjian, Wuhan Medical Center for Women and Children, Wuhan, Hubei Province, China
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