Kinetics of oxytocin effects on amygdala and striatal reactivity vary between women and men

Accumulating evidence suggests that intranasal oxytocin (OXT; 24 IU) reduces amygdala responses to fear-related stimuli in men, while exerting inverse effects in women. However, OXT enhances activity of the brain reward system in both sexes. Importantly, a crucial and still open question is whether there are sex-specific dose-response relationships for the amygdala and striatal regions. To address this question, a total of 90 healthy women participated in a double-blind, placebo-controlled crossover functional magnetic resonance imaging (fMRI) study and the results were compared with our previous findings from men. Participants were randomly assigned to three doses of OXT (6 IU, 12 IU, and 24 IU) and completed an emotional face recognition task including fearful and happy faces of varying emotional intensities. Across doses, OXT enhanced amygdala reactivity to low fearful faces compared to placebo and increased responses to happy faces in the dorsal striatum in women. While treatment effects on amygdala reactivity were evident at each given dose, the OXT effect on striatal responses to social stimuli was more pronounced with higher doses, but this dose-dependent effect did not survive correction for multiple comparisons. Importantly, OXT effects on amygdala and striatal activation significantly differed between sexes and striatal baseline sexual-dimorphic response patterns were diminished after administration of OXT. Our findings suggest that OXT increases the salience of social signals by strengthening the sensitivity for these signals in the amygdala and in the striatum in women, while OXT may primarily induce anxiolysis by reducing amygdala responses in men.