By Hera Choi, James Hagerty, Ananya Narasimhan, Elyza Ramirez, Rana Sherkat, Karen Bales, Logan Savidge, Academic Editors
Acknowledgement: We offer our sincerest appreciation to Dr. Karen Bales and Logan Savidge for their continued guidance and support throughout our writing process for this literature review. The edits and remarks provided on their behalf not only allowed us to polish up the paper, but also gave us many opportunities to learn more about the nature of the prairie voles we work with. We would also like to thank the editors of the Aggie Transcript for providing us excellent feedback, tools, and edits to bring us to our finished literature review.
Prairie voles are a monogamous rodent species that exert a variety of human-like social behaviors. Voles are often used as animal models to study certain behavioral patterns in humans. This paper attempts to review the neurobiology of prairie vole pair-bonding. Hormones such as oxytocin and vasopressin are known to have biological effects on prairie vole pair-bonding development. We hypothesize that the introduction of oxytocin and vasopressin may facilitate behaviors such as aggression since it has been revealed that pair-bonding highly impacts social behavioral displays.
Microtus ochrogaster, commonly known as the prairie vole, exhibits many similar behavioral patterns to humans, including biparental care, alloparenting (the presence of non-breeding male and female voles participating in pup care), pair-bonding, and social attachment. As such, prairie voles have been used widely in studies investigating various mental health disorders, namely autism spectrum disorder, depression, addiction, and schizophrenia, providing researchers with more information on human behaviors related to cognition, parenting, and interpersonal relationships . This review aims to demonstrate that pair-bond formation, in conjunction with the hormones oxytocin and vasopressin, aids prairie vole social development. Although these conclusions can be made with current research, further research should can address limitations such as including more female prairie voles in these studies and comparing oxytocin uptake between both sexes.
Prairie voles live in communal groups, typically consisting of males and females with their offspring . Pair-bonding between male and female prairie voles can facilitate the biparental care of their offspring as opposed to monoparental care. As a biparental species, both male and female prairie voles divide postpartum parental activities relatively equally. Both maintain and build their nest, cache food, lick, groom, and brood pups . The only parental activity strictly maternal is the nursing of pups . Biparental care is not the only form of parenting that vole pups can receive. Parenting styles can also vary in duration of contact and the presence of alloparental care. Extended family lines often exist, in which juveniles remain in the natal nest as alloparents .
Once a male and female pair form an established pair-bond, they remain socially monogamous. A standard method of measuring a pair-bond in animals in the lab is partner preference testing, or measuring the mate’s preference for their partner over a stranger of the opposite sex. Through partner preference testing, researchers have demonstrated that injecting high doses of oxytocin (OT) or vasopressin (AVP) is associated with the development of a pair-bond in both male and female prairie voles . Antagonists of OT or AVP receptors interfere with pair-bond formation, further supporting that both OT and AVP are necessary for pair-bonding behaviors . AVP also regulates nonresident males’ exclusion by the resident male, also known as mate-guarding, further maintaining the pair-bond between the resident male and female vole .
Social monogamy is a characteristic that is rarely seen in the animal kingdom. Critical hormones combined with prairie voles’ social environment make these coinciding behaviors possible.
The Role of Hormones in Affiliative Behaviors
Although hormones do not directly cause behavioral changes by influencing the three behavioral components (sensory systems, central nervous systems, and effectors), hormones can increase the possibility that appropriate responses will be expressed in response to certain stimuli . Studies have aimed to reveal mechanisms in which hormones act on pair-bonding behavior. Receptor autoradiographic binding procedures, in which radioactive molecules are attached to ligands to visualize receptor distributions, showed higher vasopressin receptor (V1aR) densities in the medial preoptic area of the brain in pair-bonded male prairie voles compared to that of sexually naïve male voles . It has been supported that the V1aR is necessary for both the formation and maintenance of pair-bonds in prairie voles, suggesting AVP has a significant role in pair-bonding behavior, particularly once male prairie voles reach sexual maturity .
However, in female prairie voles, AVP inhibition appears to have little effect on altering pair-bonding behaviors. Instead, the use of oxytocin receptor antagonist, ornithine vasotocin (OTA), results in inhibition of partner preference formation . It has been demonstrated that the administration of OT with dopamine (DA) can induce partner preference without mating in female prairie voles [8,9]. Some studies have expanded on the role of OT and DA in pair-bond formation, revealing that the presence of OT and DA D2-type receptors in the nucleus accumbens (NAcc), the mediator of motivation and action, are both vital in pair-bond formation in female voles . This is further supported by findings that have determined a positive correlation between affiliative behavior and oxytocin receptor density within the NAcc [11,12]. High concentrations of both OT and DA D2-type receptors within the NAcc suggest that affiliative behaviors and pair-bonding are extremely rewarding for female prairie voles.
While the effects of AVP and OT inhibition on vole pair-bonding behavior are well studied, there have also been studies that have looked at the direct impact of administration of these hormones. Through partner preference testing, researchers have demonstrated that injecting high doses of AVP or OT is associated with the development of a pair-bond in both male and female prairie voles . However, it has been shown that AVP administration to juvenile male voles can later result in impediments in partner preference formation . Similar to what was observed in adult female voles, treatment of OT during the neonatal stage significantly decreases the display of partner preference-related behaviors in female voles . These findings demonstrate possible dual effects of a single hormone determined by the dose, age, and duration of administration.
The Role of Hormones in Social Aggression
Social recognition is an integral component of prairie vole behavior, permitting this species to distinguish one conspecific from another for protection, inbreeding avoidance, monogamous mate selection, and comfort . Aggression or affiliation displays are based on the lack or presence of recognition, respectively, likely mediated by oxytocin receptors (OXTR) . Prairie voles commonly show aggression towards non-familiar individuals, especially after forming a pair-bond with another vole . In many species of mammals, gonadal hormones have a prominent role in mate guarding and mating-related aggression . However, it has been supported in prairie voles that the removal of gonads has little effect in decreasing aggression [17,18]. Instead, AVP and OT, rather than gonadal hormones, appear to control aggressive behaviors in prairie voles. For example, injection of AVP in adult male prairie voles increases intermale aggression. Meanwhile, developmental exposures of AVP can induce post-mating-like aggressive behaviors in sexually naïve males . Sexually dimorphic roles are also present in aggression behaviors, with AVP administration having less effects on aggression in female voles. AVP receptor antagonists do block female aggression, highlighting the need for AVP receptors in aggression behaviors, even in female voles .
Aggression in female voles and its mechanisms have not been studied as extensively as it is in males. There are indications that OT may play a significant role in female vole aggressive behaviors. Females treated with OT following weaning show increased intrasexual aggression, while males treated with the same procedures are not affected . Developmental OT treatment also results in decreased social behaviors in female voles . Overall, further investigation on the effects of OT on male prairie vole guarding and aggression as opposed to female prairie voles is needed to make comparative conclusions.
Vole Behavior and Hormones
This review looked in depth at prairie vole behaviors related to the hormones AVP and OT. Together, both hormones induce social behaviors in male and female prairie voles, particularly those related with affiliation and pair-bonding. It is important to note that hormonal treatment may result in very different effects based on the developmental stage of the voles, the dosage of hormones, and the surrounding environment. This may be particularly important when experimenting with voles across multiple developmental stages, but this has yet to be studied. Further research should investigate whether AVP and OT have differential effects on prairie vole development, as hormonal influences tend to change over time.
In all behavioral aspects, including aggression and pair-bonding, sexual dimorphism was observed in response to specific hormone inhibitors and hormone treatments. AVP has been found to be more important for adult male prairie vole pair-bonding, whereas OT and DA are necessary for pair-bonding in adult female voles. However, the effects of AVP and OT become more complex depending on when additional injections have been administered during the prairie vole’s life. Although AVP is significant for male prairie vole pair-bonding, administration during the juvenile stage can actually impair the formation of partner preferences. This effect is also seen in neonatal females, but with OT and not AVP. The difference in hormonal physiology may be a factor in the sexually dimorphic behaviors we see in the two sexes, though more research is needed for conclusive remarks. It may also suggest that the neurobiology between males and females is different from one another, at least in the aspect of pair-bonding.
A general trend that was discovered was that there had been more research done regarding male prairie voles. Due to the fact that the two sexes of voles show dimorphic behaviors, it is important to study both sexes of voles separately to prevent generalization of prairie vole neurobiology.
Prairie voles have become valuable organisms through which we can observe many aspects of human behavior. Although prairie vole neurobiology is incredibly complex, it paves the way for more research to be done to clarify the link between hormonal activity and behavior for both prairie voles and humans alike. Further routes of research that we suggest are quantifying the relationship between AVP receptors and aggression in female voles, since current studies mostly address this relationship in males. Similarly, we can address the effect of OT on intrasexual aggression in male prairie voles to comparatively study the effects of OT between sexes. Research of these factors may also be enhanced by including trials on prairie voles of different developmental stages to study the long-term outcomes of these hormones on behavior. Overall, our hypothesis linking OT and AVP to the neurobiology of pair-bonding and subsequent behaviors is supported by the literature, but there are many gaps to fill regarding the comprehensive impact of these hormones and pair-bonding on social displays and behavior between both sexes and across developmental stages.
- McGraw, L., & Young, L. 2010. The prairie vole: an emerging model organism for understanding the social brain. Trends In Neurosciences. 33(2): 103-109. Doi: =10.1016/j.tins.2009.11.006
- Carter, C. S., & Getz, L. L. 1993. Monogamy and the Prairie Vole. Scientific American. 268(6):100–106.
- Thomas, J. A., & Birney, E. C. 1979. Parental Care and Mating System of the Prairie Vole, Microtus ochrogaster. Behavioral Ecology and Sociobiology. 5(2): 171–186.
- Roberts, R., Zullo, A., & Carter, C. 1997. Sexual Differentiation in Prairie Voles: The Effects of Corticosterone and Testosterone. Physiology & Behavior. 62(6): 1379-1383. doi: 10.1016/s0031-9384(97)00365-x
- Cho, M. M., De Vries, A. C., Williams, J. R., & Carter. C. S. 1999. The Effects of Oxytocin and Vasopressin on Partner Preferences in Male and Female Prairie Voles (Microtusochrogaster). Behavioral Neuroscience. 113(5): 1071-1079. doi:10.1037//0735-7044.113.5.1071
- Nelson, R. J., & Kriegsfeld. L. J. 2018. An Introduction to Behavioral Endocrinology (5th ed). Massachusetts : Siauner.
- Gobrogge, K. L., Liu, Y., Young, L. J., & Wang, Z. 2009) Anterior Hypothalamic Vasopressin Regulates Pair-Bonding and Drug-Induced Aggression in a Monogamous Rodent. PNAS. 106(45): 19144-19149. doi:10.1073/pnas.0908620106
- Insel, T. R., & Hulihan, T. J. 1995. A Gender-Specific Mechanism for Pair Bonding: Oxytocin and Partner Preference Formation in Monogamous Voles. Behavioral Neuroscience,\. 109(4): 782-789.
- Williams, J. R., Catania, K. C., & Carter, S. 1992. Development of Partner Preferences in Female Prairie Voles (Microtus ochrogaster): The Role of Social and Sexual Experience. Hormones and Behavior. 26: 339-349.
- Liu, Y., & Wang, Z. X. (2003). Nucleus Accumbens Oxytocin and Dopamine Interact to Regulate Pair Bond Formation in Female Prairie Voles. Neuroscience, 121, 537-544. doi:10.1016/S0306-4522(03)00555-4
- Olazábal, D. E., & Young, L. J. (2006a). Oxytocin receptors in the nucleus accumbens Facilitate “spontaneous” maternal behavior in adult female prairie voles. Neuroscience, 141(2), 559–568. https://doi.org/10.1016/j.neuroscience.2006.04.017
- Olazábal, D. E., & Young, L. J. (2006b). Species and individual differences in juvenile Female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum. Hormones and Behavior, 49(5), 681–687. https://doi.org/10.1016/j.yhbeh.2005.12.010
- Ross, H. E., & Young, L. J. (2009). Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Frontiers in Neuroendocrinology, 30(4), 534–547. https://doi.org/10.1016/j.yfrne.2009.05.004
- Simmons, T. C., Balland, J. F., Dhauna, J., Yang, S. Y., Traina, J. L., Vazquez, J., & Bales, L. (2017). Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult Male Prairie Voles (Microtus ochrogaster). Frontiers in Endocrinology, 8: 145. doi:10.3389/fendo.2017.00145
- Bales, K., Westerhuyzen, J. A. V., Lewis-Reese, A. D., Grotte, N. D., Lanter, J. A., Carter, S. (2007). Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles, Hormones and Behavior, 52 (2), 274-279. doi: 10.1016/j.yhbeh.2007.05.004.
- Blocker, T. D., & Ophir, A. G. 2015. Social recognition in paired but not single male prairie voles. Animal Behaviour. 108: 1–8. doi:10.1016/j.anbehav.2015.07.003
- Demas, G. E., Moffatt, C. A., Drazen, D. L., & Nelson, R. J. 1999. Castration Does not Inhibit Aggressive Behavior in Adult Male Prairie Voles (Microtus ochrogaster). Physiology & Behavior. 66(1): 59-62.
- Bowler, C. M., Cushing, B. S., & Carter, C. S. 2002. Social Factors regulate Female-Female Aggression and Affiliation in Prairie Voles. Physiology & Behavior. 76: 559-566.
- Stribley, J. M., & Carter, S. 1999. Developmental Exposure to Vasopressin Increases Aggression in Adult Prairie Voles. PNAS. 96(22): 12601-12604.
- Bales, K. L., Carter, C. S. 2003. Sex Differences and Developmental Effects of Oxytocin on Aggression and Social Behavior in Prairie Voles (Microtus ochrogaster). Hormones and Behavior. 44: 178-184. doi:10.1016/S0018-506X(03)00154-5
- Arias del Razo, R., & Bales, K. L. 2016. Exploration in a dispersal task: Effects of early experience and correlation with other behaviors in prairie voles ( Microtus ochrogaster). Behavioural Processes, 132, 66–75. doi: 10.1016/j.beproc.2016.10.002
- Carter, C. S., & Roberts, R. L. 1997. The psychobiological basis of cooperative breeding in rodents. In N. G. Solomon & J. A. French (Eds.). Cooperative breeding in mammals. Cambridge University Press. 231-236.
- DeVries, A. C., DeVries, M. B., Taymans, S., & Carter, C. S. 1995. Modulation of pair bonding in female prairie voles (Microtus ochrogaster) by corticosterone. Proceedings of the National Academy of Sciences, 92(17): 7744–7748. doi: 10.1073/pnas.92.17.7744
- Donaldson, Z. R., Spiegel, L., & Young, L. J. 2010. Central Vasopressin V1a Receptor Activation is Independently Necessary for Both Partner Preference Formation and Expression in Socially Monogamous Male Prairie Voles. Behavioral Neuroscience, 124(1): 159-163. doi:10.1037/a0018094