Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles

Curr Biol. 2022 Mar 14;32(5):1026-1037.e4. doi: 10.1016/j.cub.2022.01.014. Epub 2022 Feb 1.


Social relationships are dynamic and evolve with shared and personal experiences. Whether the functional role of social neuromodulators also evolves with experience to shape the trajectory of relationships is unknown. We utilized pair bonding in the socially monogamous prairie vole as an example of socio-sexual experience that dramatically alters behaviors displayed toward other individuals. We investigated oxytocin-dependent modulation of excitatory synaptic transmission in the nucleus accumbens as a function of pair-bonding status. We found that an oxytocin receptor agonist decreases the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in sexually naive virgin, but not pair-bonded, female voles, while it increases the amplitude of electrically evoked EPSCs in paired voles, but not in virgins. This oxytocin-induced potentiation of synaptic transmission relies on the de novo coupling between oxytocin receptor signaling and endocannabinoid receptor type 1 (CB1) receptor signaling in pair-bonded voles. Blocking CB1 receptors after pair-bond formation increases the occurrence of a specific form of social rejection-defensive upright response-that is displayed toward the partner, but not toward a novel individual. Altogether, our results demonstrate that oxytocin's action in the nucleus accumbens is changed through social experience in a way that regulates the trajectory of social interactions as the relationship with the partner unfolds, potentially promoting the maintenance of a pair bond by inhibiting aggressive responses. These results provide a mechanism by which social experience and context shift oxytocinergic signaling to impact neural and behavioral responses to social cues.

Keywords: CRISPR; context; endocannabinoids; experience; monogamous; oxytocin; pair bond; partner preference; social rejection; ventral striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arvicolinae / metabolism
  • Female
  • Grassland
  • Humans
  • Nucleus Accumbens* / metabolism
  • Oxytocin / pharmacology
  • Pair Bond
  • Receptors, Oxytocin* / metabolism
  • Social Behavior


  • Receptors, Oxytocin
  • Oxytocin