Aggression has many uses and causes in animals, and many different species display aggression in a wide range of contexts. In some species females use aggression for the same reason as their male counterparts - in defense or acquisition of resources (Been et al., 2019; Duque-Wilckens and Trainor, 2017). This could be performing aggression in defense of a territory (Goymann et al., 2008; Rosvall, 2008), in defense of a mate (Bales and Carter, 2003; Bowler et al., 2002; Goymann et al., 2008), or to maintain dominance status (Lord et al., 2021; McCann et al., 2017). Many studies investigating the neuroendocrine mechanisms of female aggression are conducted in rodents, and in the most commonly studied rodent species females do not defend territories but will exhibit aggression to defend pups (Lonstein and Gammie, 2002) or for mating opportunities (Aubry et al., 2022; Newman et al., 2019). There has been greater success in studying non-traditional rodent species like the pair bonding prairie vole (Bales and Carter, 2003; Bowler et al., 2002) and the Syrian (Faruzzi et al., 2005; Payne and Swanson, 1970; Solomon et al., 2007) and Siberian hamsters where females readily engage in aggression (Munley et al., 2022; Ren et al., 2020; Rendon et al., 2017; Rendon and Demas, 2016). Thus, there is strong evidence that females across a variety of species engage in aggressive behavior. An important question is how engaging in aggressive behavior impacts the neuroendocrine system.

An extensive literature has outlined how engaging in aggressive encounters alters brain and behavior in male vertebrates (Marler and Trainor, 2020). In male California mice (Peromyscus californicus), winning aggressive encounters triggers a transient increase in testosterone levels and more enduring increases in androgen receptor expression in the mesolimbic dopamine system (Fuxjager et al., 2009, Fuxjager et al., 2010). These changes are thought to contribute to what is dubbed the winner-challenge effect, wherein animals' increased aggression occurs following winning experiences thus allowing an individual to win future aggressive encounters (Oyegbile and Marler, 2005). Similar results have been reported in humans (Carré, 2009; Casto and Edwards, 2016). Comparatively less is known about how winning experiences affect female brain and behavior. Female California mice demonstrated shorter attack latencies across three consecutive resident-intruder tests but showed no changes in other aggressive behaviors (Silva et al., 2010). While male California mice show higher testosterone levels after winning an encounter, females have lower plasma levels of progesterone (Davis and Marler, 2003) and higher levels of oxytocin (OXT) and corticosterone (Trainor et al., 2010) after winning aggressive encounters. These data show that there are important differences in how engaging in aggression affects males and females. Increases in corticosterone could represent an energy mobilization response. However, males offensively attack more often than females (this manuscript) and males have less of a corticosterone increase than females. This suggests that engaging in aggression may trigger a strong physiological stress response for females. The increased corticosterone finding in particular suggests that engaging in aggression generates a stronger stress response in females than males. Interestingly, this same pattern is found when females are socially defeated (Trainor et al., 2013) with the females also showing social withdrawal after defeat. Recent work in outbred Swiss Webster mice demonstrates that engaging in aggressive behavior is reinforcing for some males while for most females engaging in aggression is not reinforcing (Aubry et al., 2022). Interestingly, outbred female CD-1 mice show stronger preferences for social interaction with other females than inbred female C57BL/6 J mice (Ramsey et al., 2022). Thus, although females can engage in aggression, there is accumulating evidence that the physiological and behavioral impacts of these experiences differ in important ways compared to males. A key question is whether these effects are context dependent. For example in male California mice, the winner effect is observed in familiar but not novel environments (Fuxjager et al., 2009). Female Mus musculus do not defend territories, leaving the question of whether aggression would be stressful or aversive to females that naturally defend territories.

California mice are a unique species of deer mouse that display monogamy and perform joint territorial aggression (Rieger et al., 2021), and females engage in aggression regardless of if pups or mates are present (Davis and Marler, 2003; Duque-Wilckens and Trainor, 2017; Silva et al., 2010). Previous work has identified time-specific relationships between aggressive interactions and progesterone, OXT, and arginine vasopressin (AVP) responses in female California mice (Davis and Marler, 2003; Steinman et al., 2015; Trainor et al., 2010). For example in one study that quantified steroid hormones one hour after females engaged in fighting, decreases in plasma progesterone but no change in circulating corticosterone was observed (Davis and Marler, 2003). When hormones were quantified immediately after engaging in aggression, females showed greater increases of corticosterone and plasma OXT (Trainor et al., 2010). Finally females that engaged in aggression did show increased c-fos expression in OXT and AVP neurons in the paraventricular nucleus (PVN) (Steinman et al., 2015). In these same studies, regions like the bed nucleus of the stria terminalis and the PVN have also been implicated in California mouse aggression. Here we focus on the PVN because AVP is primarily synthesized in his region (Caldwell et al., 2008), and because AVP in this region has already been implicated in California mice neural response to stress (De Jong et al., 2013; Steinman et al., 2015; Trainor et al., 2010). However, little is known about the impacts of aggression on the brains and behavior of females compared to what we know about male California mouse aggression. The primary goals of this study are to identify how female residents responded to intruders, and to find how previously identified neuropeptide neurons OXT and AVP change in response to aggression within the PVN.