Septal oxytocin administration impairs peer affiliation via V1a receptors in female meadow voles

Abstract

The peptide hormone oxytocin (OT) plays an important role in social behaviors, including social bond formation. In different contexts, however, OT is also associated with aggression, social selectivity, and reduced affiliation. Female meadow voles form social preferences for familiar same-sex peers under short, winter-like day lengths in the laboratory, and provide a means of studying affiliation outside the context of reproductive pair bonds. Multiple lines of evidence suggest that the actions of OT in the lateral septum (LS) may decrease affiliative behavior, including greater density of OT receptors in the LS of meadow voles that huddle less. We infused OT into the LS of female meadow voles immediately prior to cohabitation with a social partner to determine its effects on partner preference formation. OT prevented the formation of preferences for the partner female. Co-administration of OT with a specific OT receptor antagonist did not reverse the effect, but co-administration of OT with a specific vasopressin 1a receptor (V1aR) antagonist did, indicating that OT in the LS likely acted through V1aRs to decrease partner preference. Receptor autoradiography revealed dense V1aR binding in the LS of female meadow voles. These results suggest that the LS is a brain region that may be responsible for inhibitory effects of OT administration on affiliation, which will be important to consider in therapeutic administrations of OT.

Keywords: Lateral septum; Meadow vole; Oxytocin; Social behavior; Vasopressin; Vasopressin 1a receptor.

Fig. 1

Effects of oxytocin infusion on partner preferences for a same-sex cage-mate. A significant preference for huddling with the partner over the stranger was observed in the aCSF group, while OT inhibited the partner preference, and significantly less time was spent huddling with the partner in the OT group compared to the aCSF group. OTRA co-administration did not block the OT-induced inhibition of the partner preference, whereas V1aRA co-administration rescued the partner preference. *p < 0.05, **p < 0.001. aCSF: artificial cerebrospinal fluid (vehicle); OT: oxytocin (1 ng); OT + OTRA: oxytocin (1 ng) + oxytocin receptor antagonist (30 ng); OT + V1aRA: oxytocin (1 ng) + vasopressin receptor antagonist (30 ng).

Fig. 2

Vasopressin 1a receptor binding in the presence and absence of a selective receptor antagonist. (A) Incubation with the radioligand [¹²⁵I]-phenylacetyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH₂. (B) Co-incubation with radioligand and an excess of unlabeled selective vasopressin 1a receptor ligand d(CH₂)₅¹[Tyr(Me)²,Arg⁸]vasopressin in an adjacent section from the same brain. Exposure time was optimized to keep lateral septum binding within the linear range of iodinated standards; in this range non-specific binding was almost undetectable.

Fig. 3

Vasopressin 1a receptor binding in the lateral septum. One representative individual (top row) displays dense V1aR binding in anterior (A) and posterior (B) sections of the LS. A second representative individual (bottom row) demonstrates the low end of observed V1aR binding in anterior (C) and posterior (D) sections of the LS, while binding in other brain regions remains consistent. Binding in the anterior LS was highest in the dorsal region, while binding was more uniform in the posterior LS.