Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
By J. Rihel, D. Prober, Anthony C. Arvanites, Kelvin T Lam, Steven R. Zimmerman, Sumin Jang, Stephen J. Haggarty, D. Kokel, L. L. Rubin, Randall T. Peterson and 1 more. Science, 2010
745 citations recorded by the source corpus.
Behavioral Profiling The complexity of the brain makes it difficult to predict how a drug will affect behavior without direct testing in live animals. Rihel et al. (p. 348) developed a high-throughput assay to assess the effects of thousands of drugs on sleep/wake behaviors of zebrafish larvae. The data set reveals a broad conservation of zebrafish and mammalian sleep/wake pharmacology and identifies pathways that regulate sleep. Moreover, the biological targets of poorly characterized small molecules can be predicted by matching their behavioral profiles to those of well-known drugs. Thus, behavioral profiling in zebrafish offers a cost-effective way to characterize neuroactive drugs and to predict biological targets of novel compounds. The effects of most neuroactive drugs are conserved and can be detected by behavioral screening. 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.
Subfields: Cell Biology, Cognitive Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/077a855bb22959c6ba1604727e968c04ee3321b1
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- Qiqing Chen
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Citations in the corpus
- Human Disease Models in Drosophila melanogaster and the Role of the Fly in Therapeutic Drug Discovery (2011, positive): “Rihel et al. (2010) have successfully developed and applied a highthroughput , quantitative screen for small molecules that could alter the locomotor behavior of larval zebrafish .”
- Measuring behavioral and endocrine responses to novelty stress in adult zebrafish (2010, neutral): “and relatively simple behavior, with a limited number of endpoint”
- Applications in image-based profiling of perturbations. (2016, neutral): “Grouping compounds by their phenotypic effects is not only feasible for static images of cells but also for videos of complex behaviour in whole organisms; the locomotor response of zebrafish correctly predicted many small molecules’ mechanism of action, some previously poorly characterized [74].”
- Quantitative investigation of the mechanisms of microplastics and nanoplastics toward zebrafish larvae locomotor activity. (2017, positive): “Behavioral response is related to neuronal and physiological integrity of the developing zebrafish, which is highly sensitive to pollutants, and has become a validated tool to evaluate the comprehensive sublethal toxic effects on zebrafish larvae (Rihel et al., 2010; MacPhail et al., 2009; Nusser et”