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Publication Detail

Title: Behavioral screening of the LOPAC1280 library in zebrafish embryos.

Authors: Vliet, Sara M; Ho, Trina C; Volz, David C

Published In Toxicol Appl Pharmacol, (2017 Aug 15)

Abstract: Spontaneous activity represents an early, primitive form of motor activity within zebrafish embryos, providing a potential readout for identification of neuroactive compounds. However, despite use as an endpoint in chemical screens around the world, the predictive power and limitations of assays relying on spontaneous activity remain unclear. Using an improved high-content screening assay that increased throughput from 384 to 3072 wells per week, we screened a well-characterized library of 1280 pharmacologically active compounds (LOPAC1280) - 612 of which target neurotransmission - to identify which targets are detected using spontaneous activity as a readout. Results from this screen revealed that (1) 8% of the LOPAC1280 library was biologically active; (2) spontaneous activity was affected by compounds spanning a broad array of targets; (3) only 4% of compounds targeting neurotransmission impacted spontaneous activity; and (4) hypoactivity was observed for 100% of hits detected, including those that exhibit opposing mechanisms of action for the same target. Therefore, while this assay was able to rapidly identify potent neuroactive chemicals, these data suggest that spontaneous activity may lack the ability to discriminate modes of action for compounds interfering with neurotransmission, an issue that may be due to systemic uptake following waterborne exposure, persistent control variation, and/or interference with non-neurotransmission-related mechanisms.

PubMed ID: 28623180 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Genetically Modified; Behavior, Animal/drug effects*; Data Mining; Embryo, Nonmammalian/drug effects; High-Throughput Screening Assays*; Motor Activity/drug effects*; Nervous System/drug effects*; Nervous System/embryology; Nervous System/metabolism; Neurotransmitter Agents/pharmacology*; Neurotransmitter Agents/toxicity; Reproducibility of Results; Small Molecule Libraries*; Synaptic Transmission/drug effects; Time Factors; Time-Lapse Imaging; Video Recording; Zebrafish/embryology*; Zebrafish/genetics; Zebrafish/metabolism

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