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

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.

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

“…This expansive LS circuitry indicates important subregional differences within the LS, corresponding to diverse or even opposing functions. The opposing function is also supported by findings that LS subregions can directly inhibit each other ( Sheehan et al, 2004 ; Leroy et al, 2018 ; Oliveira et al, 2021 ). During our review of the literature, we were able to differentiate studies that specifically target one of the above four LS subregions; however, others likely target two or more of these subregions.…”

Consequences of pandemic-associated social restrictions: Role of social support and the oxytocin system

“…Primarily synthesized in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus OXT is released not only into the peripheral circulation, but also within distinct brain regions in response to various social stimuli in male and female individuals ( Grinevich and Neumann, 2020 , Jurek and Neumann, 2018 , Landgraf and Neumann, 2004 , Neumann, 2009 , Neumann and Landgraf, 1989 ). Local OXT receptor-mediated signaling, in turn, is essential for the fine-tuned regulation of social behaviors including sexual, maternal, aggressive and juvenile play-fight behaviors, pair-bonding, social cognition and naturally occurring social preference behavior shown in rats, mice, voles and other mammals ( Lukas et al, 2011b , Menon et al, 2018 , Oettl et al, 2016 , Oliveira et al, 2021 , Zoicas et al, 2014 , Bosch and Young, 2018 , Donaldson and Young, 2008 , Jong and Neumann, 2018 , Jurek and Neumann, 2018 ). Of specific interest in this context is the finding that OXT neurons are even responsive to subtle social stimuli such as social investigation, auditory social stimuli and social touch in mice and rats, resulting in increased central release ( Marlin et al, 2015 , Menon et al, 2018 , Tang et al, 2020b , Zoicas et al, 2014 ).…”

Novel competition test for food rewards reveals stable dominance status in adult male rats

“…Importantly, future studies should investigate whether social hierarchy could be assessed in female rats using the modified Food Competition Task. The neural mechanisms of female dominance and aggression have been surprisingly overlooked, and most of the knowledge in this direction has been obtained in the context of maternal aggression 43 – 45 , with some notable exceptions 46 , 47 , moment where females display robust, clear and strong aggressive episodes. However, established social rank, contrary to de novo establishment of social hierarchies, is not based in aggressive encounters.…”