Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

The study demonstrated that in late pregnancy, the neurosteroid allopregnanolone induced opioid inhibition of the hypothalamus–pituitary–adrenal (HPA) axis responses to stressors, such as interleukin-1β (IL-1β), in rats. This was achieved by auto-inhibiting noradrenaline release in the paraventricular nucleus (PVN). Inhibition of the enzyme 5α-reductase with finasteride restored HPA axis responses to IL-1β, indicating that allopregnanolone was responsible for the attenuation of stress responses. The study also found increased activity of allopregnanolone-synthesizing enzymes in the hypothalamus during late pregnancy. Naloxone, an opioid antagonist, restored HPA responses, further supporting the role of allopregnanolone in mediating opioid inhibition. This mechanism may have implications for the regulation of other brain systems during pregnancy.