Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
Abstract
A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go–related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors.
Additional Information
© 2010 American Association for the Advancement of Science. Received for publication 8 October 2009. Accepted for publication 11 December 2009. We thank J. Dowling, D. Milan, and G. Vanderlaan for suggestions and reagents and D. Schoppik, G. Uhl, and I. Woods for critical reading of the manuscript. Supported by a Bristol-Myers Squibb postdoctoral fellowship of the Life Sciences Research Foundation (J.R.), a Helen Hay Whitney Foundation postdoctoral fellowship (D.A.P.), a NIH Pathway to Independence grant (D.A.P.), the Stanley Medical Research Institute (S.J.H.), the Harvard Stem Cell Institute (L.L.R.), NIH grants MH086867 and MH085205 (R.T.P.), and grants from NIH and the McKnight Endowment Fund for Neuroscience (A.F.S.). L.L.R. is a founder of iPierian Inc., a biotechnology company, and is a member of its scientific advisory board.Attached Files
Accepted Version - nihms178948.pdf
Supplemental Material - Rihel.SOM.pdf
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Additional details
- PMCID
- PMC2830481
- Eprint ID
- 60230
- Resolver ID
- CaltechAUTHORS:20150914-145343001
- Bristol-Myers Squibb
- Life Sciences Research Foundation
- Helen Hay Whitney Foundation
- NIH Pathway to Independence
- Stanley Medical Research Institute
- Harvard Stem Cell Institute
- NIH
- MH086867
- NIH
- MH085205
- McKnight Endowment Fund for Neuroscience
- NIH
- Created
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2015-09-15Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field