A primitive social circuit: vasotocin–substance P interactions modulate social behavior through a peripheral feedback mechanism in goldfish

At its core, the polyvagal theory proposes that peptides affect simple social behaviors through influences on hindbrain autonomic processes. To test this mechanism, we compared the effects of fore‐ and hindbrain infusions of vasotocin (VT) on social approach behavior in goldfish. VT infusions into the 4th ventricle, which ink infusions verified did not move rostrally to the forebrain, inhibited social approach at a lower dose than did infusions into the 3rd ventricle, which did diffuse to the hindbrain. Thus, VT actions in the hindbrain appear to modulate this simple social behavior. We then identified a population of substance P (SP)‐immunoreactive cells in the hindbrain that are encapsulated by putative VT terminals, and determined that those cells project to the periphery. Injecting SP peripherally, as with infusing VT centrally, inhibited social approach, and peripheral injections of an SP antagonist, but not central infusions, abolished the behavioral effects of central VT infusions. We therefore propose that VT inhibits social approach by activating SP cells in the hindbrain, which then induce changes in body state that feed back to the brain. Central VT infusions did not inhibit feeding, suggesting that this VT mechanism selectively affects appetitive social responses. Because VT projections to the hindbrain are highly conserved in vertebrates, influences on peripheral feedback processes like the one we have described in goldfish may reflect how VT affected simple social behaviors in ancestral vertebrates and thus preadapted members of this peptide family to play increasingly complex roles in social and emotional regulation in modern animals.