Oral Oxytocin Facilitates Responses to Emotional Faces in Reward and Emotional-Processing Networks in Females

Abstract

Introduction: Oxytocin (OXT) is proposed as a potential therapeutic peptide for social dysfunction due to its modulatory actions on socioemotional regulation in humans. While the majority of studies have used intranasal OXT administration, we have recently shown that oral (lingual spray), but not intranasal, administration can significantly enhance activity of the brain reward system in response to emotional faces in males; however, its effects on females are unknown. Methods: Seventy healthy females participated in the current randomized, placebo-controlled, pharmaco-imaging clinical trial, and the results were compared with our previous data from 75 males who underwent the same protocol. Participants were randomly assigned to OXT (24 IU) or placebo (PLC) groups and completed an implicit emotional face paradigm (angry/fear/happy/neutral) where they were only required to identify face gender. Results: In line with previous results in males, oral OXT significantly increased plasma OXT concentration changes and enhanced putamen responses to all emotional faces compared to PLC in females. Additionally, OXT increased left amygdala activity to happy and angry faces and enhanced putamen-superior temporal gyrus functional coupling during processing of happy faces in females which was significantly different from males. Conclusion: Our findings suggest that oral OXT enhances responses in both reward and emotional-processing networks in females as well as males, and additionally, in females, it strengthens coupling between reward and social cognition regions.