Oxytocin receptor is not required for social attachment in prairie voles

Abstract

Prairie voles are among a small group of mammals that display long-term social attachment between mating partners. Many pharmacological studies show that signaling via the oxytocin receptor (OxtR) is critical for the display of social monogamy in these animals. We used CRISPR-mutagenesis to independently generate three different OxtR null mutant prairie vole lines. OxtR mutants displayed social attachment such that males and females showed a behavioral preference for their mating partners over a stranger of the opposite sex when assayed using different paradigms. Mothers lacking OxtR delivered viable pups, and parents displayed care of their young and raised them to the weanling stage. Together, our studies unexpectedly reveal that OxtR-mediated signaling is genetically dispensable for social attachment, parturition, and parental behavior.

Effects of Oxytocin Receptor Blockade on Dyadic Social Behavior in Monogamous and Non-MonogamousEulemur

“…Overall, the variability in our findings may also indicate d) an increasingly uncertain role of oxytocin in mating bonds (Grebe et al, 2021;Berendzen et al, 2022).…”

“…The copyright holder for this this version posted September 17, 2022. ; https://doi.org/10.1101/2022.09.14.507945 doi: bioRxiv preprint receptor blockade prevents partner preference formation in this same species (Cho et al, 1999; but see Berendzen et al, 2022). Neuroethological and neuroanatomical studies of the prairie vole have fostered a dominant paradigm for investigating the biological mechanisms underlying pairbond formation and maintenance (reviewed in Walum & Young, 2018).…”

“…Indeed, a series of high-profile failures to replicate published findings on the hormone’s putative psychobehavioral effects in humans (e.g., trust: Nave et al, 2015; empathy/memory: Tabak et al, 2019; social interaction in children with autism: Sikich et al, 2021) has spurred recent scrutiny of oxytocin research more generally (see Mierop et al, 2020). Additionally, heterogeneity both within and between animal models regarding neuropeptide-mediated behavior (e.g., Madrid et al, 2020; Berendzen et al, 2022) and neurocircuitry (Phelps & Young, 2003; Grebe et al, 2021) underscores the need for robust, comparative approaches to both establish generalizable principles and identify disparate features of oxytocin’s social functions.…”

Rethinking the Architecture of Attachment: New Insights into the Role for Oxytocin Signaling

“…Such tools generally rely on knockdown, or the reduction in expression of a given gene, or knockout, the complete loss of expression of a targeted gene. Given the central role of oxytocin signaling in affiliative and parental behaviors across taxa, we and other groups adapted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based molecular genetic tools to generate prairie voles that lack the oxytocin receptor (Oxtr; Horie et al, 2019;Berendzen et al, 2022). We examined partner preference following cohabitation for one week with an opposite sex partner using the established assay described above (Beery, 2021;Williams et al, 1992).…”

“…We examined partner preference following cohabitation for one week with an opposite sex partner using the established assay described above (Beery, 2021;Williams et al, 1992). We made the surprising finding that Oxtr is genetically dispensable for pair bond formation, as partner preference was maintained in Oxtr knockout animals (Berendzen et al, 2022). Horie et al, 2019 examined a different subset of behaviors commonly attributed to oxytocinergic regulation, including pup vocalization, anxietylike behavior, alloparental behavior (parental behavior exhibited by individuals towards non-descendant young), and sociability.…”