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Eur Neuropsychopharmacol. 2017 Sep 23. pii: S0924-977X(17)30906-9. doi: 10.1016/j.euroneuro.2017.09.004. [Epub ahead of print]

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

Author information

1
Department of Neuroscience, Psychology and Behaviour, University of Leicester, University Rd, Leicester, LE1 7RH, UK.
2
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main, Germany; Division of Neuropsychopharmacology, Department of Psychology, University of Tartu, Ravila 14A, Tartu 50411, Estonia.
3
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main, Germany.
4
Department of Genetics and Genome Biology, University of Leicester, University Rd, Leicester LE1 7RH, UK.
5
Centre for Developmental and Biomedical Genetics, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
6
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main, Germany. Electronic address: Andreas.Reif@kgu.de.
7
Department of Neuroscience, Psychology and Behaviour, University of Leicester, University Rd, Leicester, LE1 7RH, UK. Electronic address: whjn1@le.ac.uk.

Abstract

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

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