<p> Infusion of 17&beta;-estradiol into the arcuate nucleus of the hypothalamus (ARH) 47.5 hours after estrogen benzoate (EB) priming rapidly facilitates sexual receptivity (lordosis) via G protein-coupled estrogen receptor 1 (GPER) that deactivates &micro;-opioid receptors (MOP) in the medial pre-optic nucleus of the hypothalamus (MPN). Initial estradiol inhibits lordosis via activating an ARH neurocircuit that activates MPN MOP, and simultaneously upregulates orphanin FQ/ nociception (OFQ/N), its cognate receptor (ORL-1), and progesterone receptor (PR) in the ARH. Subsequent ORL-1 activation 48 hours post-EB deactivates MPN MOP to facilitate lordosis. Thus, I hypothesized that GPER directly regulates OFQ/N neurons and tested whether EB increased coexpression of GPER and OFQ/N in ARH neurons. EB significantly increased the number of GPER OFQ/N expressing neurons. Antiestrogens, tamoxifen (TAM) and ICI 182,780 (ICI), are treatments for some estrogen responsive tumors, but sometimes exacerbate tumor proliferation via GPER. I hypothesized that TAM and ICI activate ARH GPER and facilitate lordosis via deactivation of MPN MOP. In EB-primed rats, ARH infusion of either TAM or ICI facilitated lordosis and deactivated MPN MOP. GPER antagonist, G15, blocked these results. Thus, TAM and ICI rapidly activate ARH GPER neurons that express OFQ/N to facilitate sexual receptivity.</p>