PUBLICATION

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

Authors

Gutiérrez, H.C., O'Leary, A., Freudenberg, F., Fedele, G., Wilkinson, R., Markham, E., van Eeden, F., Reif, A., Norton, W.H.J.

ID

ZDB-PUB-170928-4

Date

2017

Source

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 30: 30-43 (Journal)

Registered Authors

van Eeden, Freek, Wilkinson, Robert

Keywords

Aggression, Anxiety, Monoamine oxidase, Mouse, Nitric oxide, Zebrafish

MeSH Terms

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

(all 19)

PubMed

28951000 Full text @ Eur Neuropsychopharmacol

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
mao	nos1^sh336/sh336	standard conditions	Adult	brain	RTPCR	Fig. 7
mao	WT	standard conditions	Adult	brain	RTPCR	Fig. 7
nos1	nos1^sh336/sh336	standard conditions	Adult	brain	ISH	Fig. 2
nos1	nos1^sh336/sh336	standard conditions	Adult	brain	RTPCR	Fig. 2
nos1	nos1^sh336/sh336	standard conditions	Adult	whole organism	WB	Fig. 1
nos1	WT	standard conditions	Adult	brain	RTPCR	Fig. 2
nos1	WT	standard conditions	Adult	brain	ISH	Fig. 2
nos1	WT	standard conditions	Adult	caudal periventricular hypothalamus	ISH	Fig. 1
nos1	WT	standard conditions	Adult	caudal thalamic nucleus	ISH	Fig. 1
nos1	WT	standard conditions	Adult	caudal tuberal nucleus	ISH	Fig. 1

1 - 10 of 30

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: selegiline hydrochloride	Adult	aggressive behavior decreased occurrence, abnormal	Fig. 8
WT	chemical treatment by environment: selegiline hydrochloride	Adult	brain monoamine oxidase activity decreased occurrence, abnormal	Fig. 8
WT	chemical treatment by environment: selegiline hydrochloride	Adult	swimming behavior decreased occurrence, abnormal	Fig. 8
WT	stress	Adult	regulation of cortisol secretion occurrence, normal	Fig. 5
WT	stress	Adult	whole organism cortisol increased amount, abnormal	Fig. 5
nos1^sh336/sh336	standard conditions	Adult	aggressive behavior decreased occurrence, abnormal	Fig. 3
nos1^sh336/sh336	standard conditions	Adult	brain mao expression increased amount, abnormal	Fig. 7
nos1^sh336/sh336	standard conditions	Adult	brain nos1 expression decreased amount, abnormal	Fig. 2
nos1^sh336/sh336	standard conditions	Adult	brain nos1 expression decreased amount, abnormal	Fig. 2
nos1^sh336/sh336	standard conditions	Adult	brain nos2b expression increased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sh336		Indel	nos1
w2		Point Mutation	mitfa

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nos1	TALEN1-nos1	TALEN

Fish

Fish
mitfa^w2/w2
nos1^sh336/sh336
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Gutiérrez et al., 2017 ZDB-PUB-170928-4 PMID:28951000

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

Gutiérrez et al., 2017

ZDB-PUB-170928-4
PMID:28951000