Budniok, S.; Callaerts-Vegh, Z.; Bakermans-Kranenburg, M.; Bosmans, G.; D'Hooge, R.

Oxytocin (OT) is a neuropeptide implicated in complex social behaviors including trust and attachment, yet the neural mechanisms underlying its effects remain unclear. OT is thought to modulate behavior by enhancing the salience of social cues and attenuating prediction error (PE) processing, the discrepancy between expected and actual outcomes that drives learning. Since both salience coding and PE processing involve dopamine (DA) neurons as well, the current study investigated the putative interdependence between OT and DA in social safety learning using the social transmission of food preference (STFP) paradigm. STFP is based on the observation that mice (observers) display neophobia toward novel food, but develop a preference for it after a conspecific demonstrator signals its safety. We interpreted STFP acquisition as a functional parallel to human trust-based learning and found that OT enhanced learning in a trust acquisition condition, but only when DA signaling was intact. In a trust violation condition, where demonstrated food was later paired with lithium chloride (LiCl)-induced food aversion, both OT and DA depletion blocked learning, resulting in retained preference for demonstrated food, but not when OT was administered under DA depletion. These findings reveal a functional interaction between the OT and DA systems to modulate social safety learning, which may have important implications for the potential of OT in treating disorders involving DA dysfunction.