Enhanced corticosterone concentrations and attenuated Fos expression in the medial amygdala of female oxytocin knockout mice exposed to psychogenic stress

Centrally released oxytocin (OT) is believed to attenuate the response of the hypothalamic-pituitary-adrenal (HPA) axis to psychogenic stress. To test this hypothesis, we measured plasma corticosterone concentrations and Fos-immunoreactive protein in the paraventricular nucleus of the hypothalamus (PVN) and limbic brain areas of female wild-type and OT knockout mice that were exposed to a shaker platform, a predominantly psychogenic stress. Plasma corticosterone concentrations after shaker stress were higher in female OT knockout mice than wild-type mice. Genotypic differences in the corticosterone response after shaker stress persisted across all stages of the estrous cycle and when mice were conditioned to repeated shaker stress. Shaker stress activated Fos in OT-positive neurons of wild-type mice and corticotropin-releasing hormone-positive, but not vasopressin-positive, neurons within the PVN of wild-type and OT knockout mice. Fos expression was also increased after shaker stress in the bed nucleus of the stria terminalis, medial and central nuclei of the amygdala, medial preoptic area, and the paraventricular nucleus of the thalamus of wild-type and OT knockout mice. However, Fos expression in the medial amygdala was significantly lower in female OT knockout mice than wild-type mice. Our findings indicate heightened stress-induced corticosterone release in female OT knockout mice. Therefore, the results suggest that OT pathways play a role in attenuating the HPA axis response to psychogenic stress in female mice.