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Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
Ist Teil von
Science (American Association for the Advancement of Science), 2010-01, Vol.327 (5963), p.348-351
Ort / Verlag
Washington, DC: American Association for the Advancement of Science
Erscheinungsjahr
2010
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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.