Effect of amniotic-fluid ingestion on vaginal–cervical-stimulation-induced Fos expression in female rats during estrus

Placental Opioid-Enhancing Factor (POEF) is a substance found in amniotic fluid (AF) that, when ingested, potentiates opioid-mediated, but not non-opioid-mediated, hypoalgesia. Vaginal–cervical stimulation (VCS) produces a stimulus-bound, partially opioid-mediated hypoalgesia that previous research has shown to be potentiated by AF ingestion. To understand the mechanism of opioid enhancement by POEF we investigated the pattern of neural activation after a bout of VCS that produced hypoalgesia, with and without co-administration of AF. Specifically, virgin Long–Evans rats showing vaginal estrus were handled briefly (control) or received VCS (75 g pressure, 1 min), in a pattern that approximated early parturition rather than copulation, using a spring-loaded glass-rod probe. Rats were given an orogastric infusion (0.25 ml) of either AF or 0.9% saline resulting in four groups (VCS or handling; AF or saline). Rats were perfused 90 min after treatment and tissue was processed by immunohistochemistry for Fos. The number of Fos-immunoreactive cells was counted in structures previously shown to express Fos in response to VCS (the medial preoptic area, MPOA; the ventrolateral portion of the ventromedial hypothalamic nucleus, vlVMH; the arcuate nucleus, ARC). We found that this pattern of VCS did not produce a significant increase in Fos expression in the MPOA and vlVMH unless it was paired with AF. VCS produced a significant increase in Fos in the ARC. The interaction of AF and VCS on Fos expression in the MPOA suggests that POEF may enhance vaginal–cervical sensory input at parturition to facilitate sensitization of the MPOA, and presumably facilitate maternal-behavior onset.

Research highlights
► Vaginal–cervical stimulation (VCS) using 75 g pressure for 1 min produces hypoalgesia.
► Amniotic fluid (AF) ingestion potentiates Fos produced by VCS.
► VCS and AF ingestion interact to increase Fos in the MPOA and VMH.
► AF ingestion did not change VCS-induced Fos expression in the arcuate nucleus.
► First experiment showing the pattern of neural activation after AF ingestion.