Department of Chemistry, University of California, Davis, Davis, California 95616, United States.
Department of Molecular Biosciences, University of California, Davis, Davis, California 95616, United States.
ACS Chem Neurosci. 2023 Mar 1;14(5):875-884. doi: 10.1021/acschemneuro.2c00642. Epub 2023 Feb 8.
In recent years, psychedelics have garnered significant interest as therapeutic agents for treating diverse neuropsychiatric disorders. However, the potential for these compounds to produce developmental neurotoxicity has not been rigorously assessed, and much of the available safety data is based on epidemiological studies with limited experimental testing in laboratory animal models. Moreover, the experimental safety data available thus far have focused on adult organisms, and the few studies conducted using developing organisms have tested a limited number of compounds, precluding direct comparisons between various chemical scaffolds. In the present study, 13 psychoactive compounds of different chemical or pharmacological classes were screened in a larval zebrafish model for teratological and behavioral abnormalities following acute and chronic developmental exposures. We found that the psychedelic tryptamines and ketamine were less neurotoxic to larval zebrafish than LSD and psychostimulants. Our work, which leverages the advantage of using zebrafish for higher throughput toxicity screening, provides a robust reference database for comparing the neurotoxicity profiles of novel psychedelics currently under development for therapeutic applications.
近年来，迷幻剂作为治疗各种神经精神疾病的治疗剂引起了广泛关注。然而，这些化合物是否具有发育神经毒性尚未经过严格评估，而且大部分可用的安全性数据基于流行病学研究，在实验室动物模型中的实验测试有限。此外，迄今为止可用的实验安全性数据主要集中在成年生物体上，并且使用发育生物体进行的少数研究测试了有限数量的化合物，因此无法在各种化学支架之间进行直接比较。在本研究中，在幼鱼斑马鱼模型中筛选了 13 种不同化学或药理学类别的精神活性化合物，以研究急性和慢性发育暴露后是否会出现致畸和行为异常。我们发现迷幻色胺和氯胺酮对幼鱼斑马鱼的神经毒性小于 LSD 和精神兴奋剂。我们的工作利用斑马鱼进行高通量毒性筛选的优势，为比较目前正在开发用于治疗应用的新型迷幻剂的神经毒性特征提供了一个强大的参考数据库。
