Assessment of the convulsant liability of antidepressants using zebrafish and mouse seizure models

Epilepsy Behav. 2011 Nov;22(3):450-60. doi: 10.1016/j.yebeh.2011.08.016. Epub 2011 Oct 1.


In the past, antidepressants have been thought to possess proconvulsant properties. This assumption remains controversial, however, because anticonvulsant effects have been attributed to certain antidepressants. To date, it remains unclear which antidepressants can be used for the treatment of patients with epilepsy with depression. The present study was designed to determine the anticonvulsant and/or proconvulsant effects of three antidepressants (citalopram, reboxetine, bupropion) against pilocarpine- and pentylenetetrazole-induced acute seizures in larval zebrafish and mice. In zebrafish, all antidepressants were anticonvulsant in the pentylenetetrazole model. In addition, citalopram was anticonvulsant in the zebrafish pilocarpine model, whereas reboxetine and bupropion were without significant effect. In mice all three antidepressants increased some thresholds for pentylenetetrazole-induced convulsive-like behaviors at varying doses, whereas thresholds for pilocarpine-induced convulsive-like behaviors were generally lowered, particularly at the highest doses tested. In general we conclude that the convulsant liability of antidepressants is model and concentration dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Antidepressive Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Convulsants / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Green Fluorescent Proteins / genetics
  • Male
  • Mice
  • Pentylenetetrazole / toxicity
  • Pilocarpine / toxicity
  • Seizures / chemically induced*
  • Seizures / drug therapy*
  • Seizures / mortality
  • Seizures / physiopathology
  • Zebrafish


  • Antidepressive Agents
  • Convulsants
  • enhanced green fluorescent protein
  • Pilocarpine
  • Green Fluorescent Proteins
  • Pentylenetetrazole