title: Orphanin FQ in the mediobasal hypothalamus facilitates sexual receptivity through the deactivation of medial preoptic nucleus mu-opioid receptors.
abstract: Sexual receptivity, lordosis, can be induced by sequential estradiol and progesterone or extended exposure to high levels of estradiol in the female rat. In both cases estradiol initially inhibits lordosis through activation of β-endorphin (β-END) neurons of the arcuate nucleus of the hypothalamus (ARH) that activate μ-opioid receptors (MOP) in the medial preoptic nucleus (MPN). Subsequent progesterone or extended estradiol exposure deactivates MPN MOP to facilitate lordosis. Opioid receptor-like receptor-1 (ORL-1) is expressed in ARH and ventromedial hypothalamus (VMH). Infusions of its endogenous ligand, orphanin FQ (OFQ/N, aka nociceptin), into VMH-ARH region facilitate lordosis. Whether OFQ/N acts in ARH and/or VMH and whether OFQ/N is necessary for steroid facilitation of lordosis are unclear. In Exp I, OFQ/N infusions in VMH and ARH that facilitated lordosis also deactivated MPN MOP indicating that OFQ/N facilitation of lordosis requires deactivation of ascending ARH-MPN projections by directly inhibiting ARH β-END neurons and/or through inhibition of excitatory VMH-ARH pathways to proopiomelanocortin neurons. It is unclear whether OFQ/N activates the VMH output motor pathways directly or via the deactivation of MPN MOP. In Exp II we tested whether ORL-1 activation is necessary for estradiol-only or estradiol+progesterone lordosis facilitation. Blocking ORL-1 with UFP-101 inhibited estradiol-only lordosis and MPN MOP deactivation but had no effect on estradiol+progesterone facilitation of lordosis and MOP deactivation. In conclusion, steroid facilitation of lordosis inhibits ARH β-END neurons to deactivate MPN MOP, but estradiol-only and estradiol+progesterone treatments appear to use different neurotransmitter systems to inhibit ARH-MPN signaling.
authors.affiliation: Department of Biological Sciences, California State University, Long Beach, Long Beach, CA 90840-9502, USA.
authors.forename: Nayna M
authors.initials: NM
authors.lastname: Sanathara
authors.forename: Justine
authors.initials: J
authors.lastname: Moraes
authors.forename: Shrey
authors.initials: S
authors.lastname: Kanjiya
authors.forename: Kevin
authors.initials: K
authors.lastname: Sinchak
mesh_terms: D000818:Animals; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011187:Posture / Q000502:physiology*; D011301:Preoptic Area; D011374:Progesterone / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans; D017450:Receptors, Opioid, mu / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D000097629:Nociceptin
chemical_list: D004958:Estradiol; D018847:Opioid Peptides; D011374:Progesterone; D017450:Receptors, Opioid, mu; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)