Significance
In the past decade, there has been an increase in studies using oxytocin (OT) for improving social cognition, but results have been inconsistent. In this study, we took advantage of the physiological relationship between the opioid and OT systems and tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions. Coadministration of OT and opioid blocker leads to supralinear enhancement of prolonged and selective attention to a live partner and increases interactive gaze after critical social events. Furthermore, we provide neurogenetic evidence in the human brain supporting the interaction between specific opioid receptor genes and the genes for OT processing. Our results suggest a new avenue for amplifying the efficacy of OT in clinical populations.Abstract
To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt. Furthermore, attention to various facial regions was differentially modulated depending on social context. Using the Allen Institute’s transcriptional atlas, we further established the colocalization of μ-opioid and κ-opioid receptor genes and OT genes at the OT-releasing sites in the human brain. These data across monkeys and humans support a regulatory relationship between the OT and opioid systems and suggest that administering OT under opioid antagonism may boost the therapeutic efficacy of OT for enhancing social cognition.
