Oxytocin and Social Relationships: From Attachment to Bond Disruption

Abstract

Social relationships throughout life are vital for well-being and physical and mental health. A significant amount of research in animal models as well as in humans suggests that oxytocin (OT) plays an important role in the development of the capacity to form social bonds, the mediation of the positive aspects of early-life nurturing on adult bonding capacity, and the maintenance of social bonding. Here, we focus on the extensive research on a socially monogamous rodent model organism, the prairie vole (Microtus ochrogaster). OT facilitates mating-induced pair bonds in adults through interaction with the mesolimbic dopamine system. Variation in striatal OT receptor density predicts resilience and susceptibility to neonatal social neglect in female prairie voles. Finally, in adults, loss of a partner results in multiple disruptions in OT signaling, including decreased OT release in the striatum, which is caused by an activation of the brain corticotropin releasing factor (CRF) system. The dramatic behavioral consequence of partner loss is increased depressive-like behavior reminiscent of bereavement. Importantly, infusions of OT into the striatum of adults prevents the onset of depressive-like behavior following partner loss, and evoking endogenous OT release using melanocortin agonists during neonatal social isolation rescues impairments in social bonding in adulthood. This work has important translational implications relevant to the disruptions of social bonds in childhood and in adults.

Keywords: Attachment; Bereavement; Grieving; Monogamy; Pair bond; Social loss.

Fig. 1

Female prairie voles with low NAc OTR are susceptible to early adversity. (a) The percentage of time females spent huddling with their partner vs total huddling significantly correlates with NAc OTR binding in the early-isolated, but not control females. (b) Only females with low OTR binding exposed to early isolation did not form a partner preference. Representative autoradiographs of (c) low and (d) high OTR NAc females. *P < 0.05 vs partner. Scale bar = 1 mm. Adapted from Barrett et al. (2015)

Fig. 2

In male prairie voles, 4–5 days of separation from the female partner, but not from a male sibling, increases passive stress-coping behavior reflected as the time being inactive, i.e., floating in the forced swim test (a, c “vehicle”) and immobile in the tail suspension test (b). Chronic infusion of synthetic OT bilaterally into the NAc shell abolishes the increased passive stress-coping after separation, whereas blocking OTR by an OTR antagonist (OTR-A) increases passive stress-coping in the non-separated males (c). **P < 0.01 vs all other groups; +P = 0.05 vs vehicle female-paired group; ##P < 0.01, #P < 0.05 vs corresponding vehicle group. (a, b) Adapted from Bosch et al. (2009), (c) Bosch et al. (2016)

Fig. 3

Schematic demonstrating our proposed model of the dynamic interaction of the brain CRF system on the OT system at multiple levels, from OT mRNA in the PVN and via OT release and OTR binding in the NAc shell to the resulting well-being when either with the partner (top) or after separation (bottom). Red arrows indicate inhibitory actions on multiple processes of the OT system by the CRF system