ZFIN ID: ZDB-PUB-090227-6
Hyperserotonergic phenotype after monoamine oxidase inhibition in larval zebrafish
Sallinen, V., Sundvik, M., Reenilä, I., Peitsaro, N., Khrustalyov, D., Anichtchik, O., Toleikyte, G., Kaslin, J., and Panula, P.
Date: 2009
Source: Journal of neurochemistry   109(2): 403-415 (Journal)
Registered Authors: Anichtchik, Oleg, Kaslin, Jan, Panula, Pertti, Peitsaro, Nina, Sallinen, Ville, Sundvik, Maria
Keywords: ontogeny, behavior, deprenyl, fluvoxamine, serotonin, PCPA
MeSH Terms:
  • Animals
  • Brain/drug effects
  • Brain/enzymology
  • Brain/growth & development
  • Larva
  • Monoamine Oxidase/metabolism*
  • Monoamine Oxidase Inhibitors/pharmacology*
  • Motor Activity/drug effects
  • Motor Activity/physiology
  • Phenotype*
  • RNA, Messenger/antagonists & inhibitors
  • RNA, Messenger/metabolism
  • Selegiline/pharmacology
  • Serotonin/metabolism*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/chemistry
PubMed: 19222706 Full text @ J. Neurochem.
5-HT and 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 serotonin 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 hpf and histochemical enzyme activity from 42 hpf. Deprenyl (100 muM) decreased MAO activity 34-74% depending on the age. Inhibition of MAO by deprenyl strongly increased serotonin but not dopamine and noradrenaline levels. Deprenyl decreased 5-HT-ir in serotonergic neurons and induced novel ectopic 5-HT-ir 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 PCPA normalized serotonin levels and rescued the behavioral alteration, indicating that the symptoms were serotonin 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.