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Modulation of Threat Response in Larval Zebrafish

  • Andrew J. Rennekamp
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1787)

Abstract

High-throughput, whole-organism phenotypic drug screening is made possible using live zebrafish larvae. Many human drugs have now been shown to affect zebrafish larvae in similar ways, through homologous molecular mechanisms. At this stage in life, zebrafish are small enough to fit in multi-well, microliter plates, yet developed enough to exhibit complex phenotypes, such as hunting behaviors and avoidance of predators. Importantly, zebrafish larvae can be easily dosed via automated pipetting of chemical compounds directly into their liquid medium, without injection. Only microgram amounts of small molecules are required, making animal husbandry and dosing regimens cost effective. This chapter describes how the stereotyped zebrafish larval responses to darkness and strobe light—which cause hyperactivity and freezing behavior, respectively—can be used to efficiently screen small molecules for brain and behavior-modulating activity.

Key words

Fear Freezing behavior CNS Whole-organism screening Phenotypic screens High-throughput drug discovery Small molecules Strobe light response 

References

  1. 1.
    Swinney DC, Anthony J (2011) How were new medicines discovered? Nat Rev Drug Discov 10:507–519CrossRefGoogle Scholar
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    Rennekamp AJ, Peterson RT (2015) 15 years of zebrafish chemical screening. Curr Opin Chem Biol 24:58–70CrossRefGoogle Scholar
  3. 3.
    Rennekamp AJ, Huang XP, Wang Y, Patel S, Lorello PJ, Cade L et al (2016) Sigma1 receptor ligands control a switch between passive and active threat responses. Nat Chem Biol 12:552–558CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineMassachusetts General HospitalBostonUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA

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