title: Assessment of the convulsant liability of antidepressants using zebrafish and mouse seizure models.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Katia
authors.initials: K
authors.lastname: Vermoesen
authors.forename: Ann-Sophie K
authors.initials: AS
authors.lastname: Serruys
authors.forename: Ellen
authors.initials: E
authors.lastname: Loyens
authors.forename: Tatiana
authors.initials: T
authors.lastname: Afrikanova
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
authors.forename: Anneleen
authors.initials: A
authors.lastname: Schallier
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Crawford
authors.forename: Camila V
authors.initials: CV
authors.lastname: Esguerra
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Ralph
authors.initials: R
authors.lastname: Clinckers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015027:Zebrafish
chemical_list: D000928:Antidepressive Agents; D003292:Convulsants; C485184:enhanced green fluorescent protein; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D010433:Pentylenetetrazole