title: Serotonin antagonists induce anxiolytic and anxiogenic-like behavior in zebrafish in a receptor-subtype dependent manner.
abstract: Motor function and anxiety-like responses are easily quantifiable in zebrafish, a novel model organism for behavioral pharmacology. Activation of serotonin receptors through the use of selective agonists has been shown to alter anxiety-like behaviors in zebrafish. However, few studies have examined the effect of blockade of specific serotonin receptors. In the current study, we examine the effect of 4 serotonin receptor antagonists selective for 5-HT1A, 5-HT1B/D, 5-HT2, and 5-HT3 receptors on zebrafish motor and anxiety-like responses. Exposure to the receptor antagonists did not change baseline motor responses. However, when placed in a novel environment, zebrafish previously exposed to GR 55562 (5-HT1B/D antagonist) exhibited reduced anxiety-like behavior, whereas zebrafish previously exposed to p-MPPF (5-HT1A antagonist), Ketanserin (5-HT2 antagonist), or Ondasetron (5-HT3 antagonist) exhibited increased anxiety-like behaviors. These results show that drugs developed for mammalian serotonin receptors are efficacious in the zebrafish too, a finding that demonstrates evolutionary conservation of the serotoninergic system. The results also imply that zebrafish may be an appropriate animal model for examining the serotonergic neurotransmitter system in vertebrates.
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada.
authors.forename: Magda
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Mississauga, Canada. Electronic address: stevenhuy.tran@mail.utoronto.ca.
authors.forename: Steven
authors.initials: S
authors.lastname: Tran
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada.
authors.forename: Arrujyan
authors.initials: A
authors.lastname: Muraleetharan
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Markovic
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada; Department of Cell and Systems Biology, University of Toronto Mississauga, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gerlai
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy; D001549:Benzamides / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D000631:Aminopyridines; D014151:Anti-Anxiety Agents; D001549:Benzamides; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; C078730:serotonin 5 receptor; C103477:3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide; D017294:Ondansetron; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine; D007650:Ketanserin
keywords: Anxiety; Behavior; Novel environment; Serotonin antagonist; Zebrafish