Loss of oxytocin receptor function disrupts neural signatures of pair bonding and fidelity in the nucleus accumbens.

Enduring relationships dramatically shape behaviors by promoting affiliation between familiar individuals; however, the neural mechanisms driving attachments remain unclear. Oxytocin receptor (Oxtr) signaling in the nucleus accumbens (NAc) reinforces pair bond formation in socially monogamous prairie voles. How Oxtr influences NAc activity during affiliative behaviors with partners and rejection of strangers is unknown. Using in vivo fiber photometry, we demonstrate that genetic loss of Oxtr sex-specifically disrupts attachment behaviors and associated NAc activity. In females, loss of Oxtr reduces prosocial behaviors and NAc activity during initial chemosensory investigation of novel males; however, partner-directed affiliative behavior and associated activity increase independently of Oxtr. In males, loss of Oxtr increases prosocial investigation of novel females, and initial behavioral and neural activity patterns predict future partner preference in Oxtr-null males. These findings reveal sex-specific roles for Oxtr in early pair bond development through modulation of prosociality and sensory processing.