Oxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats

Vinícius Elias De Moura Oliveira,Hannah Nora Wolf,Inga D Neumann,Veronica Egger,Trynke R De Jong,Valery Grinevich,Alexandra Lorenz,Michael Lukas,Anna-Lena Mayer,Elisa Durante,Oliver J Bosch,Anna Bludau

doi:10.1038/s41467-021-23064-5

Abstract

In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialysis approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), is required for aggression in female rats. Accordingly, increased activity of putative OXT receptor-positive neurons in the vLS, and decreased activity of putative AVP receptor-positive neurons in the dLS, are likely to underly aggression in female rats. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data suggest a model showing that septal release of OXT and AVP differentially affects aggression in females by modulating the inhibitory tone within LS sub-networks.

Highlights

Alexandra Lorenz 1, Anna-Lena Mayer 1, Anna Bludau 1, Oliver J
Aiming to study neural mechanisms of aggression in virgin female rats, we have established a behavioral paradigm combining social isolation and aggression-training by repeated exposure to the female intruder test (FIT), which reliably exacerbated the mild levels of aggression typically displayed by GH female Wistar rats
We have shown that female aggression is controlled by a fine-tuned balance between OXT, arginine vasopressin (AVP), and GABA neurotransmission within two distinct neuronal populations of the lateral septum (LS), i.e., the dorsal LS (dLS) and ventral LS (vLS), with contrasting subregional effects of OXT and AVP (Fig. 8)

Summary

Introduction

Alexandra Lorenz 1, Anna-Lena Mayer 1, Anna Bludau 1, Oliver J. We established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). To better understand the neurobiology of aggression and to develop potential treatment options, laboratory animal models of aggression have been successfully used for decades[1,3,4] These models were mostly developed in male rodents, whereas females have been rather understudied, except during the physiologically unique period of lactation[5]. We investigated the role of oxytocin (OXT) and arginine vasopressin (AVP) in the aggressive behavior displayed by female

Methods

Results

Conclusion