Hypothalamo-pituitary-adrenal (HPA) axis responses to stress are compromised in disease states but under selected circumstances responses are also altered in healthy physiological states, such as during reproduction. Corticosterone secretion is attenuated in response to physical and psychological stressors in late pregnancy, parturition and lactation and may provide protection for the offspring from long term adverse effects of glucocorticoids and alter metabolic processes, balancing energy requirements of the mother and offspring. Since in the rat and mouse the responses of hypothalamic paraventricular neurones and selected inputs are also attenuated, central mechanisms underlie the HPA axis hyporesponsiveness in late pregnancy. However, enhanced glucocorticoid feedback cannot explain the adaptations in responsiveness to stress (1), as it can in disease states such as depression. We have investigated whether the attenuated responses to stress are mediated by two key central systems that regulate HPA axis responses in rats: oxytocin and monoamines. Central oxytocin inhibits the HPA axis in virgin rats, and central oxytocin release and receptor expression are enhanced in late pregnancy and parturition; however, increased oxytocin inhibition does not explain the attenuated HPA axis responses (2). In contrast, monoamines such as noradrenaline strongly drive paraventricular (PVN) neurone responses to stress. Using a combination of neuropharmacological, neuroanatomical and microdialysis studies, we have shown that noradrenergic inputs to the PVN are reduced and that PVN neurones are less sensitive to noradrenaline in late pregnancy (3), in response to swimming- or IL1β-induced stress. The opioid antagonist, naloxone partially restores HPA axis responses to stress and administered directly into the PVN also restores noradrenaline release. Thus, opioids presynaptically restrain the noradrenergic input to the HPA axis (4), contributing to the stress hyporesponsiveness. Therefore, profound adaptations occur in the brain during pregnancy to facilitate maternal accommodation of the fetus(es), and stress hyporesponsiveness, including underlying reduced noradrenergic signalling, persists into lactation (5). In summary, attenuation of the noradrenergic system underlies attenuated HPA axis responses perinatally, and is so far the only reported central transmitter mechanism that can explain hyporesponsiveness of the HPA axis at this time.