title: Hyperserotonergic phenotype after monoamine oxidase inhibition in larval zebrafish.
abstract: Serotonin (or 5-hydroxytryptamine; 5-HT) and monoamine oxidase (MAO) are involved in several physiological functions and pathological conditions. We show that the serotonergic system and its development in zebrafish are similar to those of other vertebrates rendering zebrafish a good model to study them. Development of MAO expression followed a similar time course as the 5-HT system. MAO expression and activity were located in or adjacent to serotonergic nuclei and their targets, especially in the ventral hypothalamus. MAO mRNA was detected in the brain from 24 h post-fertilization and histochemical enzyme activity from 42 h post-fertilization. Deprenyl (100 microM) decreased MAO activity 34-74% depending on the age. Inhibition of MAO by deprenyl strongly increased 5-HT but not dopamine and noradrenaline levels. Deprenyl decreased 5-HT-immunoreactivity in serotonergic neurons and induced novel ectopic 5-HT-immunoreactivity neurons in the diencephalon in a manner dependent on 5-HT uptake. Deprenyl administration decreased locomotion, altered vertical positioning and increased heart rate. Treatment with p-chlorophenylalanine normalized 5-HT levels and rescued the behavioral alteration, indicating that the symptoms were 5-HT dependent. These findings suggest that zebrafish MAO resembles mammalian MAO A more than MAO B, metabolizing mainly 5-HT. Applications of this model of hyperserotonergism include pharmacological and genetic screenings.
authors.affiliation: Neuroscience center, Institute of Biomedicine/Anatomy, University of Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Sallinen
authors.forename: Maria
authors.initials: M
authors.lastname: Sundvik
authors.forename: Ilkka
authors.initials: I
authors.lastname: Reenilä
authors.forename: Nina
authors.initials: N
authors.lastname: Peitsaro
authors.forename: Denis
authors.initials: D
authors.lastname: Khrustalyov
authors.forename: Oleg
authors.initials: O
authors.lastname: Anichtchik
authors.forename: Gabija
authors.initials: G
authors.lastname: Toleikyte
authors.forename: Jan
authors.initials: J
authors.lastname: Kaslin
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D007814:Larva; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D012642:Selegiline; D012701:Serotonin; D008995:Monoamine Oxidase