Functional New World monkey oxytocin forms elicit an altered signaling profile and promotes parental care in rats

Abstract

The neurohormone oxytocin is a key player in the modulation of reproductive and social behavioral traits, such as parental care. Recently, a correlation between different forms of oxytocin and behavioral phenotypes has been described in the New World Monkeys (NWMs). Here, we demonstrate that, compared with the Leu⁸OXT found in most placental mammals, the Cebidae Pro⁸OXT and <i>Saguinus</i> Val³Pro⁸OXT taxon-specific variants act as equi-efficacious agonists for the G_q-dependent pathway but are weaker agonists for the β-arrestin engagement and subsequent endocytosis toward the oxytocin receptor (OXTR). Upon interaction with the AVPR1a, Pro⁸OXT and the common Leu⁸OXT yielded similar signaling profiles, being equally efficacious on G_q and β-arrestin, while Val³Pro⁸OXT showed reduced relative efficacy toward β-arrestin. Intranasal treatment with either of the variants increased maternal behavior and also promoted unusual paternal care in rats, as measured by pup-retrieval tests. We therefore suggest that Val³Pro⁸OXT and Pro⁸OXT are functional variants, which might have been evolutionarily co-opted as an essential part of the adaptive genetic repertoire that allowed the emergence of taxon-specific complex social behaviors, such as intense parental care in the Cebidae and the genus <i>Saguinus</i>.