Successful reproduction is key to a species’ evolutionary success. To increase the survival chances of offspring, many species exhibit varying degrees of parental behavior. In approximately 90% of species, uniparental care predominates, with mothers providing the primary support to offspring (1, 2). In rodents, maternal care includes nutritional provisioning through lactation, along with a range of behaviors such as kyphosis/crouching to facilitate nursing and licking/grooming pups to aid in urination and defecation (2). Other maternal behaviors that dramatically increase the survival of the offspring include the defense of the pups against potential threats like an intruding conspecific (maternal aggression) and retrieving pups into the nest when they move away from it (pup retrieval) (3). These behaviors depend on coordinated neuroendocrine changes in the mother’s brain, with neuropeptides such as oxytocin (OT) and arginine-vasopressin (AVP) playing central roles (4). While oxytocin (OT) has been extensively studied in relation to parturition and maternal bonding, AVP is increasingly recognized as a critical modulator of maternal care, maternal aggression, and social memory (for a review see (5–7).

AVP is synthesized in the hypothalamus and acts centrally via V1a and V1b receptors (8). Among these, the V1a receptor (V1aR) has been repeatedly implicated in regulating social behaviors across species, particularly in males (9). In male rodents, AVP signaling via V1aR contributes to aggression, social recognition, and pair bonding (10–13). In female rats, evidence suggests that AVP may suppress lordosis (14) and interact with OT to shape sexual receptivity (15). While the effects of AVP on male sexual behavior appear limited, it appears to inhibit female lordosis in several species (16). The involvement of AVP in sexual behavior has been explored in several species. For instance, AVP modulates sexual vocalizations in male squirrel monkeys (17) and several aspects of copulatory behaviors in mice of both sexes (18). In Syrian hamsters (Mesocricetus auratus), AVP strongly influences aggression, flank marking, and other aspects of social communication (19, 20). Photoperiodic manipulations that reduce reproductive activity are also associated with changes in V1aR binding in brain regions regulating sociosexual behavior (21). In humans, AVP enhances recognition of sexual cues in males, suggesting a role in anticipatory rather than consummatory sexual behaviors (22). These findings highlight the complexity of V1aR contributions to sexual signaling and suggest that its role in female reproduction may be species- and context-dependent.

In addition to sociosexual and affiliative behaviors, AVP and V1aR has been linked to maternal behavior. Manipulations of V1aR in rats, mice, and voles have demonstrated its involvement in maternal responsiveness, pup-directed care, and maternal aggression. During the peripartum and lactation periods, AVP mRNA expression, receptor density, and binding are elevated (23). High maternal licking and grooming behavior correlates with increased V1aR density in the lateral septum of female mice (24). Infusion of a V1aR antagonist into the medial preoptic area (MPOA) delays the onset of maternal care (25), highlighting the importance of this receptor, although early interpretations attributed this to cross-talk of AVP to OT receptors. More recent studies support a distinct, OT-independent role for AVP in maternal care (4) and maternal aggression (26) in rats. This role has been replicated in other rodent species (27, 28) and in mammals more broadly (29, 30). Unlike OT, local AVP release into the MPOA and bed nucleus of the stria terminalis (BNST) increases during the display of maternal care and mother-pup interactions in rats (31). Although AVP levels in the BNST may not sharply increase with maternal behavior, the region houses AVP-synthesizing neurons and V1aR, which are upregulated during lactation (32, 33). While V1aR signaling in the BNST does not seem essential for ongoing pup retrieval and nursing, it is implicated in maternal aggression, which serves to protect the offspring (34). Elevated V1aR mRNA expression has been reported in the amygdala, SON, and lateral septum of postpartum multiparous rats compared to primiparous controls (23, 35). Maternal aggression, but not maternal care, is reduced following microinjection of a V1aR antagonist into the BNST of Brattleboro rats, suggesting region-specific regulation of maternal behaviors (36). Fluctuations in V1aR in several important regions of the central nervous systems appear to modulate maternal aggression during the peripartum period (37). Collectively, these findings suggest that V1aR contributes to maternal caregiving and aggression across rodent models.

Here, we investigated female sexual behavior and early postpartum maternal care in Syrian hamsters lacking V1aR, generated using CRISPR-Cas9 gene editing (38). Syrian hamsters have been extensively used in studies of social neuroscience because of their well-described patterns of social behaviors, which are strongly regulated by AVP (39). Syrian hamsters provide a valuable model because their maternal care is brief and energetically constrained compared to that of mice and rats, and maternal cannibalism is relatively common (40, 41). Unlike other rodents, maternal care in hamsters is often brief and energetically constrained, suggesting specialized neuroendocrine regulation. We previously observed altered aggression and social communication in V1aRKO hamsters of both sexes (38). Based on prior findings linking V1aR to maternal care and sociosexual signaling, we hypothesized that V1aR deletion would selectively impair sexual receptivity and maternal caregiving. By testing both copulatory interactions and pup-directed behaviors in V1aR KO, heterozygous (Het), and wild-type (WT) females, this study expands our understanding of the role of AVP in female reproductive behavior and highlights the species-specific contributions of V1aR to maternal investment.

In this study, we tested the hypothesis that V1aRs contribute to the regulation of sexual and maternal behavior. Although our results did not show an effect of V1aR deletion on the overall duration of lordosis behavior in female hamsters, the genotype of the female hamster significantly influenced male mating behavior, with males displaying fewer and shorter mounting attempts when paired with females lacking one or both copies of the Avpr1a gene. Interestingly, no differences were observed in male thrusting or anogenital sniffing, which may explain why copulation itself was unaffected by genotype, as evidenced by similar pregnancy success rates and pup numbers at weaning ( Supplementary Figure 1 ). In addition to the effects on sexual behavior, V1aR deletion significantly altered maternal behavior, with KO females showing an overall reduction in pup-directed behavior and increased non-maternal behaviors. Specifically, AVP seems to modulate active maternal caregiving behaviors like licking and grooming the pups, as shown by our results. Despite spending similar amounts of time in the nest, V1aRKO females engaged less in maternal care, suggesting a selective caregiving deficit rather than general disinterest. Across the early postpartum period, KO females exhibited significantly increased locomotor activity, burrowing, and time off the nest compared with WT and Het females, whereas Het females showed a modest increase in self-grooming, the functional significance of which remains unclear. The increased burrowing behavior of V1aRKO females may reflect enhanced nesting activity; however, when considered alongside the increased locomotor activity, it could also indicate a form of anxiety-like behavior (47). Further analysis is needed to clarify the meaning of these behavioral changes. It is important to note that our CRISPR-Cas9 knockout strategy deletes Avpr1a globally, meaning that V1aR is absent not only in the brain but also in peripheral tissues such as vasculature and kidney, where it normally contributes to cardiovascular regulation, fluid balance, and stress responses (9). While we did not observe overt peripheral deficits, future work should address whether peripheral physiological consequences of V1aR loss emerge under stress or challenge conditions. Given our focus on maternal and sexual behavior, the most parsimonious explanation for our findings is that they arise from loss of V1aR signaling within brain regions critical for sociosexual behavior.

In female hamsters, sexual receptivity is primarily expressed via vaginal marking and lordosis, although these behaviors are not always co-expressed (48–50). Lordosis, in particular, facilitates intromission by arching the back and elevating the hindquarters and perhaps also blocking aggressive behavior in female hamsters, which are notoriously aggressive when not in estrus (51–53). Although we found no effect of V1aR deletion on overall lordosis duration, several studies support a role for AVP, and specifically V1aR, in this behavior. For instance, infusion of a V1aR antagonist in ventral pallidum of estradiol-primed female rats increases lordosis frequency, suggesting that AVP may have an inhibitory role (54). In agreement with this finding, systemic AVP administration also reduces lordosis (15), suggesting that AVP may act as a brake on female sexual behavior. The reduced lordosis after AVP administration may be due to the interaction with OT, as OT administration can reverse this effect (15). Conversely, exposure to short photoperiods (<12.5h of light/day), which induce anestrus, is associated with reduced V1aR binding in many brain regions important in sociosexual behavior (21), indicating complex interactions between photoperiod, AVP signaling, and sexual receptivity. The absence of lordosis differences in our V1aRKO groups may reflect compensatory mechanisms by other neuroendocrine systems, such as OT, during development.

An unexpected finding in our study was that V1aRKO females retained normal fertility: they conceived at similar rates to WT females, and produced comparable litter sizes and sex ratios. This outcome is intriguing in light of work showing that AVP, acting through V1aR, contributes to regulation of the preovulatory luteinizing hormone (LH) surge in female mice (55). Our results suggest that in Syrian hamsters, the LH surge and ovulation can proceed in the absence of V1aR signaling, perhaps through compensatory activation of oxytocin or V1b receptors, or species-specific differences in hypothalamic regulation of gonadotropin release. Thus, while V1aR is clearly important for aspects of sexual signaling and maternal care, its role in the neuroendocrine control of ovulation may be redundant or less critical in this species. Future studies that directly measure LH release in V1aRKO females will be necessary to clarify the contribution of AVP signaling to fertility.

Intriguingly, males showed a specific reduction in mounting behavior when paired with Het or KO females. No changes were observed in other behaviors such as thrusting or anogenital sniffing, which have been associated with sexual satiety and individual recognition, respectively (50, 56). The specific reduction in mounting behavior, therefore, suggests that males may be able to detect subtle differences in female cues that do not disrupt consummatory behavior once interaction begins. In rodents, males rely heavily on olfactory signals, both volatile odors and non-volatile chemosignals, to assess female receptivity. V1aR may influence the composition or detectability of these signals, perhaps through altered neuroendocrine pathways. Prior research shows that V1aR knockout or antagonism reduces pre-copulatory behavior and alters social signaling, including scent marking (21, 38). Additionally, V1aR may affect female behavioral cues such as approach or pacing, which in turn influence male mounting behavior. Even when lordosis behavior is preserved, these subtler social cues can strongly impact male mounting behavior. Brain regions such as the lateral septum, where V1aR is expressed, are known to modulate sensory detection and social responses (57). Notably, we observed that Het and KO females frequently moved away immediately after the male ceased investigating or mounting, which may account for the observed reduction in mounting behavior and is consistent with the higher locomotion duration in the KO group. However, the high variability in male and female interactions (e.g., males often exhibit intermittent mounting or cease mating at different times, and some females display early aggression that prevents mounting) made systematic quantification difficult; future studies may consider alternative approaches to capture these subtle behavioral differences. While the role of AVP in female sexual behavior remains incompletely understood, our findings suggest that AVP may influence female sexual signaling in ways that indirectly affect male behavior. Alternatively, AVP may contribute to the maintenance or consistency of lordosis posture, and its absence could subtly disrupt behavioral feedback loops during courtship and mating.

Our results also show that V1aR deletion significantly reduces maternal behavior while sparing other behaviors, aligning with existing literature. In rodents, AVP acting via V1aR has been shown to facilitate maternal responsiveness, particularly in regions such as the MPOA and the BNST, both critical hubs for maternal behavior (2, 58, 59). Further, V1aR expression correlates with licking/grooming and nursing behaviors, with increased expression correlated to naturally high licking and grooming dams (60). In agreement with this, V1aR antagonism or knockdown leads to decreased nurturing behaviors in lactating rats (2). Additionally, reduced V1aR binding in the MPOA has been linked to lower levels of maternal-pup contact and fewer nurturing postures (2). Although most prior work has focused on mice and rats, similar patterns emerge across species. In prairie voles, for example, central V1aR activation promotes pup retrieval and nesting, while V1aR disruption impairs maternal responses (61). Interestingly, in our study, V1aRKO females showed increased burrowing and locomotor activity, which may reflect a shift in behavioral priorities or disinhibition of exploratory drive. AVP is implicated in arousal regulation and behavioral gating (62), so V1aR loss may dysregulate these processes. Importantly, the increase in non-maternal activity co-occurred with decreased maternal behavior, indicating that V1aRKO females shifted their behavioral output away from pup-directed care toward other activities, despite spending similar amounts of time in the nest. This distinction supports the idea that V1aR regulates affiliative behaviors independently of overall motor activity (2). Together, these results suggest that V1aR is a critical regulator of maternal care in Syrian hamsters, likely acting through conserved neural circuits that govern social and parental behaviors across species. Our data further highlight the behavioral selectivity of V1aR signaling, which may offer insights into the nuanced neuropeptide regulation of parental investment and the evolution of care-giving strategies in mammals.

In summary, our findings demonstrate that V1aR knockout in female Syrian hamsters selectively alters key facets of social and reproductive behavior, without broadly impairing sociosexual behavior. Copulatory behavior and nest occupancy were preserved, yet KO females showed reductions in subtle aspects of sexual signaling, reflected in decreased male mounting responses, and exhibited markedly less active maternal care, particularly pup licking and grooming. At the same time, V1aRKO females displayed elevated non-maternal behaviors such as burrowing and self-grooming, suggesting a shift in behavioral priorities rather than a simple loss of maternal responsiveness. Taken together, these findings indicate that V1aR contributes selectively to certain components of sexual communication and maternal caregiving, while also modulating the balance between caregiving and other behaviors. Future studies should examine how V1aR deletion shapes the underlying neural circuits governing this behavioral allocation, as well as their involvement in human disorders characterized by social and maternal behaviors, such as postpartum depression. A deeper understanding of V1aR’s role in affiliative behavior could inform both evolutionary models and translational treatments targeting social behavior.