Orphanin FQ in the mediobasal hypothalamus facilitates sexual receptivity through the deactivation of medial preoptic nucleus mu-opioid receptors

► Lordosis requires deactivation of medial preoptic nucleus μ-opioid receptors (MOP). ► Estradiol-only (E) acts through orphanin FQ activation of ORL-1 to deactivate MOP. ► Estradiol + progesterone (E + P) MOP deactivation does not require orphanin FQ. ► E and E + P signaling converges on arcuate nucleus β-endorphin neurons. ► E and E + P use different neurotransmitters to inhibit MOP and facilitate lordosis.