Interdependency between oxytocin and dopamine in trust-based learning in mice

Oxytocin (OT) is a neuropeptide implicated in complex social behaviors such as trust and attachment, yet the neural mechanisms underlying its effects remain unclear. OT is thought to modulate behavior by enhancing 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), we investigated OT and DA interdependency in social safety learning using the social transmission of food preference (STFP) paradigm. In STFP, mice overcome neophobia towards novel food 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 demonstrated food preference in a trust acquisition condition, but only when DA signaling was intact. In a trust violation condition, the expectation of food safety was violated by pairing demonstrated food with lithium chloride (LiCl)-induced aversion. Updating was blocked after OT administration and non-significantly reduced after DA depletion, resulting in a continued preference for demonstrated food. However, this effect was absent when OT was administered under DA depletion. These findings reveal a functional interaction between the OT and DA systems in social safety learning, which may have important implications for OT's potential in treating disorders involving DA dysfunction.