학술논문

Developmental Neurotoxicity Screen of Psychedelics and Other Drugs of Abuse in Larval Zebrafish (Danio rerio)
Document Type
article
Source
ACS Chemical Neuroscience. 14(5)
Subject
Analytical Chemistry
Biochemistry and Cell Biology
Biological Sciences
Medicinal and Biomolecular Chemistry
Chemical Sciences
Neurosciences
Good Health and Well Being
Animals
Hallucinogens
Zebrafish
Larva
Ketamine
Models
Animal
Behavioral abnormalities
hallucinogens
psychoplastogens
psychostimulants
teratology
Biochemistry and cell biology
Analytical chemistry
Medicinal and biomolecular chemistry
Language
Abstract
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.