Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures

Dis Model Mech. 2012 Nov;5(6):773-84. doi: 10.1242/dmm.010090. Epub 2012 Jun 21.


The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca(2+)) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / analysis*
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Central Nervous System / drug effects
  • Central Nervous System / embryology
  • Central Nervous System / pathology
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / pathology
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Epilepsy / physiopathology
  • Gene Expression Regulation, Developmental / drug effects
  • In Situ Hybridization
  • Larva / drug effects
  • Motor Activity / drug effects
  • Muscles / drug effects
  • Muscles / embryology
  • Muscles / metabolism
  • Muscles / pathology
  • Organ Specificity / drug effects
  • Organ Specificity / genetics
  • Pentylenetetrazole
  • Picrotoxin / toxicity
  • Small Molecule Libraries / analysis
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / physiology*


  • Anticonvulsants
  • Small Molecule Libraries
  • Picrotoxin
  • Pentylenetetrazole