ABSTRACT: 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.
