Raphe serotonin neuron‐specific oxytocin receptor knockout reduces aggression without affecting anxiety‐like behavior in male mice only

Serotonin and oxytocin influence aggressive and anxiety‐like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesize...

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Published in:Genes, brain and behavior brain and behavior, 2015-02, Vol.14 (2), p.167-176
Main Authors: Pagani, J. H., Williams Avram, S. K., Cui, Z., Song, J., Mezey, É., Senerth, J. M., Baumann, M. H., Young, W. S.
Format: Article
Language:English
Subjects:
Aggression - physiology
Animals
Anxiety
Anxiety - metabolism
Behavior
Behavior, Animal
Conditional knockout
Female
Male
maternal aggression
Maternal Behavior - physiology
Mice, Knockout
Neurons
Neurons - metabolism
oxytocin
Oxytocin - metabolism
Receptors, Oxytocin - deficiency
Receptors, Oxytocin - genetics
Receptors, Oxytocin - metabolism
Rodents
Serotonin
Serotonin - metabolism
Serotonin Plasma Membrane Transport Proteins - metabolism
Sex Characteristics
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Summary:Serotonin and oxytocin influence aggressive and anxiety‐like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety‐like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open‐field, olfactory habituation/dishabituation or, surprisingly, anxiety‐like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident‐intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety‐like behaviors or maternal care. Raphe serotonin neuron‐specific oxytocin receptor knockout reduces aggression without affecting anxiety‐like behavior in male mice only
ISSN:1601-1848
1601-183X
DOI:10.1111/gbb.12202