Allopregnanolone Induces Opioid Inhibition of Hypothalamo-Pituitary-Adrenal Axis Responses to Interleukin-1β in Pregnancy

In this study, researchers investigated the role of allopregnanolone (AP) and opioids in modulating the hypothalamo-pituitary-adrenal (HPA) axis response to interleukin-1β (IL-1β) during late pregnancy. They found that in pregnant rats, the HPA axis response to IL-1β was suppressed, which was linked to the actions of AP and endogenous opioids. By using finasteride to block AP production and naloxone as an opioid antagonist, they observed that both treatments partially restored the adrenocorticotropic hormone (ACTH) response to IL-1β in pregnant rats, suggesting that AP and opioid actions were not independent. In virgin rats, AP treatment reduced ACTH responses, but naloxone restored the response, indicating that AP induced opioid tone. Additionally, AP treatment increased proenkephalin-A (pENK-A) mRNA expression in the nucleus tractus solitarius (NTS), suggesting that AP-induced opioid inhibition of HPA responses in pregnancy might be mediated through up-regulated pENK-A expression in the NTS.