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Publication Detail
Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, Schier AF
  • Publication date:
    15/01/2010
  • Pagination:
    348, 351
  • Journal:
    Science
  • Volume:
    327
  • Issue:
    5963
  • Country:
    United States
  • PII:
    327/5963/348
  • Language:
    eng
  • Keywords:
    Algorithms, Animals, Anti-Inflammatory Agents, Behavior, Animal, Calcium Channel Blockers, Calcium Channels, L-Type, Cluster Analysis, Cytokines, Drug Discovery, Ether-A-Go-Go Potassium Channels, High-Throughput Screening Assays, Larva, Motor Activity, Potassium Channel Blockers, Psychotropic Drugs, Rest, Signal Transduction, Sleep, Small Molecule Libraries, Wakefulness, Zebrafish, Zebrafish Proteins
  • Notes:
    PMCID: PMC2830481
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.
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