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Nat Chem Biol. 2016 Jul;12(7):559-66. doi: 10.1038/nchembio.2097. Epub 2016 May 30.

Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.

Author information

1
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
2
Teleos Therapeutics, Medford, Massachusetts, USA.
3
Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
4
Department of Systems Biology, Harvard Medical School, Charlestown, Massachusetts, USA.
5
Broad Institute, Cambridge, Massachusetts, USA.
6
Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
7
Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
8
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
9
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
10
NeuroBehavior Laboratory, Harvard NeuroDiscovery Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.
11
Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
12
Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.
13
NIMH Psychoactive Drug Screening Program, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.
14
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.

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 on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can 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 zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action.

PMID:
27239787
PMCID:
PMC4912417
DOI:
10.1038/nchembio.2097
[Indexed for MEDLINE]
Free PMC Article

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