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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.

SUBMITTER: Rihel J 

PROVIDER: S-EPMC2830481 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.

Rihel Jason J   Prober David A DA   Arvanites Anthony A   Lam Kelvin K   Zimmerman Steven S   Jang Sumin S   Haggarty Stephen J SJ   Kokel David D   Rubin Lee L LL   Peterson Randall T RT   Schier Alexander F AF  

Science (New York, N.Y.) 20100101 5963


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 p  ...[more]

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