Oromucosal administration of oxytocin and its receptor antagonist atosiban respectively increase and decrease preferential attention to dynamic social stimuli in men

Background: Reduced concentrations of the neuropeptide oxytocin can occur in disorders with social dysfunction, notably autism. However, the role of peripheral endogenous oxytocin concentrations and increased ones following exogenous administration in modulating key social behaviors in humans is still unclear. Here we investigated effects of targeting peripheral oxytocin receptors through oromucosal administration of oxytocin and an oxytocin receptor antagonist (atosiban) on social attention. Methods: We carried out a pre-registered, randomized, double-blind, placebo-controlled experiment with 250 adult male subjects in five treatment groups (placebo + placebo, placebo + 24 IU OT, placebo + 48 IU OT, atosiban + placebo, and atosiban + 24 IU OT), each receiving two oromucosal (lingual) administrations separated by 15 minutes. Following treatment, subjects performed an autism-sensitive dynamic social versus geometric pattern eye-tracking paradigm. Pre- and post-treatment blood samples were collected for oxytocin measurement. Results: Results showed that 48IU but not 24IU oxytocin significantly increased preferential viewing of social stimuli relative to placebo, and effects were associated with, and mediated by, increased oxytocin concentrations and negatively correlated with subjects autism quotient scores. On the other hand, atosiban reduced preference for social stimuli relative to placebo even after subsequent administration of 24IU oxytocin. Conclusions: Our findings suggest that both exogenous and endogenous oxytocin can act via peripheral receptors to enhance interest in social relative to non-social stimuli, possibly influencing the brain via acting on G[q]-coupled receptors in the vagal system. This further supports the therapeutic potential of oxytocin for social dysfunction.