Nitric oxide interacts with monoamine oxidase to modulate aggression and anxiety-like behaviour

Eur Neuropsychopharmacol. 2020 Jan;30:30-43. doi: 10.1016/j.euroneuro.2017.09.004. Epub 2017 Sep 23.


Nitric oxide (NO) is a gaseous neurotransmitter that has important behavioural functions in the vertebrate brain. In this study we compare the impact of decreased nitric NO signalling upon behaviour and neurobiology using both zebrafish and mouse. nitric oxide synthase mutant (nos1-/-) zebrafish show significantly reduced aggression and an increase in anxiety-like behaviour without altered production of the stress hormone cortisol. Nos1-/- mice also exhibit decreased aggression and are hyperactive in an open field test. Upon reduction of NO signalling, monoamine neurotransmitter metabolism is reduced as a consequence of decreased Monoamine oxidase activity. Treatment of nos1-/- zebrafish with the 5-HT receptor 1A agonist 8-OH-DPAT rescues aggression and some aspects of anxiety-like behaviour. Taken together, the interplay between NO and 5-HT appears to be critical to control behaviour. Our cross-species approach challenges the previous notion that reduced neuronal NOS leads to increased aggression. Rather, Nos1 knock-out can also lead to decreased aggression in some situations, a finding that may have implications for future translational research.

Keywords: Aggression; Anxiety; Monoamine oxidase; Mouse; Nitric oxide; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects
  • Aggression / physiology*
  • Aggression / psychology
  • Animals
  • Animals, Genetically Modified
  • Anxiety / metabolism*
  • Anxiety / psychology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / deficiency*
  • Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Agonists / pharmacology
  • Zebrafish


  • Monoamine Oxidase Inhibitors
  • Serotonin 5-HT1 Receptor Agonists
  • Nitric Oxide
  • Serotonin
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • Monoamine Oxidase