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

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 Leu(8)OXT found in most placental mammals, the Cebidae Pro(8)OXT and Saguinus Val(3)Pro(8)OXT taxon-specific variants act as equiefficacious agonists for the Gq-dependent pathway but are weaker agonists for the beta-arrestin engagement and subsequent endocytosis toward the oxytocin receptor (OXTR). Upon interaction with the AVPR(1)a, Pro(8)OXT and the common Leu(8)OXT yielded similar signaling profiles, being equally efficacious on Gq and beta-arrestin, while Val(3)Pro(8)OXT showed reduced relative efficacy toward beta-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 Val(3)Pro(8)OXT and Pro(8)OXT 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 Saguinus. (AU)