Zebrafish behavioral profiling identifies multi-target antipsychotic-like compounds

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Author
Bruni, Giancarlo
Velenich, Andrea
McCarroll, Matthew
Gendelev, Leo
Fertsch, Ethan
Taylor, Jack
Lakhani, Parth
Lensen, Dennis
Evron, Tama
Lorello, Paul J.
Huang, Xi-Ping
Kolczewski, Sabine
Carey, Galen
Prinssen, Eric
Roth, Bryan L.
Keiser, Michael J.
Kokel, David
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nchembio.2097Metadata
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Bruni, G., A. J. Rennekamp, A. Velenich, M. McCarroll, L. Gendelev, E. Fertsch, J. Taylor, et al. 2016. “Zebrafish behavioral profiling identifies multi-target antipsychotic-like compounds.” Nature chemical biology 12 (7): 559-566. doi:10.1038/nchembio.2097. http://dx.doi.org/10.1038/nchembio.2097.Abstract
Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping, and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action based on their behavioral profiles alone. Although zebrafish (Danio rerio) behaviors have been used to rapidly identify neuroactive compounds, it remains unclear exactly what kind of behavioral assays might be necessary to identify multi-target compounds such as antipsychotics. Here, we developed a battery of behavioral assays in larval zebrafish to determine if behavioral profiles could provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated animals could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multi-target mechanisms of action.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912417/pdf/Terms of Use
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