1 Scientific RepoRts | 7:40589 | DOI: 10.1038/srep40589 www.nature.com/scientificreports oxytocin biases men but not women to restore social connections with individuals who socially exclude them Xiaolei Xu, shuxia Yao, Lei Xu, Yayuan Geng, Weihua Zhao, Xiaole Ma, Juan Kou, Ruixue Luo & Keith M. Kendrick We normally react to individuals who exclude us socially by either avoiding them or increasing our attempts to interact with them. the neuropeptide oxytocin can promote social bonds and reduce social confict and we therefore investigated whether it facilitates more positive social responses towards individuals who exclude or include us. In a double-blind, placebo-controlled, between-subject design 77 healthy Chinese male and female participants received intranasal oxytocin (40 IU) or placebo before playing a modifed virtual ball-tossing game with three fctitious partners who either showed exclusion, inclusion or neutral behavioral interactions with them. Results showed that both male and female subjects threw the ball more often to individuals who excluded rather than included them, although oxytocin did not alter this or awareness/feelings of exclusion or inclusion. However, when subjects returned a week later males, but not females, in the oxytocin group exhibited an increased liking for, and preference for playing again with, players who had previously excluded them. This oxytocin efect was positively associated with independent traits. Our fndings suggest that in a collectivist culture oxytocin may promote the desire of males, but not females, with a stronger independent orientation to rebuild social connections with individuals who have previously excluded them. Being excluded or rejected is an aversive and painful social experience even when observing others sufering from it 1,2 . Te pain caused by rejection has been shown to share common brain networks including the neural alarm system and somatosensory areas which respond to physical pain 3–5 . Previous studies have shown that social rejec- tion threatens individuals’ fundamental needs, such as belonging, self-esteem, control and having a meaningful existence 6 . Te negative efect of social rejection even impacts cognitive function, for example performance in a saccade task 7 , and increased ability to detect response conficts 8 . Te aversive experience imposed by social rejection results in immediate and long-term threats to feelings of belonging 9,10 . Tus, rejected individuals tend to rebuild social bonds with others to satisfy their needs to belong 11 , become more sensitive to cues signaling potential social exclusion, such as fake smiles, and avoid being excluded in other social interaction situations 12 . Previous studies have demonstrated that the hypothalamic neuropeptide oxytocin (OXT) plays a critical role in promoting social bonds and prosocial behaviors 13,14 and can also reduce social confict 15 . Importantly, OXT can have anxiolytic efects in terms of reducing stress and anxiety in human and other animal species 16–19 and may have therapeutic potential for anxiety disorders 20,21 . However, while OXT can act as an anxiolytic and appears to reduce amygdala responses to fear-evoking stimuli 22–24 , consistent with it facilitating either tolerance or avoidance of negative emotional situations, it can in some circumstances enhance reactivity towards and memory for them and therefore potentially trigger greater approach and conciliatory behavior 25,26 . Tus, OXT might potentially play a role either in facilitating greater tolerance or avoidance by subjects of individuals who reject them socially, or alternatively facilitate greater approach towards them in an attempt to rebuild positive social connections. Tis might particularly be infuenced by cultural diferences with members of Asian collectivist cultures being more likely to respond positively towards excluders rather than rejecting them and reacting less strongly to social Key Laboratory for neuroinformation, center for information in Medicine, School of Life Science and technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China. Correspondence and requests for materials should be addressed to K.M.K. (email: k.kendrick.uestc@gmail.com) Received: 17 November 2015 accepted: 09 December 2016 Published: 12 January 2017 opeN