title: Modulation of the arcuate nucleus-medial preoptic nucleus lordosis regulating circuit: a role for GABAB receptors.
abstract: Estradiol rapidly activates a microcircuit in the arcuate nucleus of the hypothalamus (ARH) that is needed for maximal female sexual receptivity. Membrane estrogen receptor-α complexes with and signals through the metabotropic glutamate receptor-1a stimulating NPY release within the ARH activating proopiomelanocortin (POMC) neurons. These POMC neurons project to the medial preoptic nucleus (MPN) and release β-endorphin. Estradiol treatment induces activation/internalization of MPN μ-opioid receptors (MOR) to inhibit lordosis. Estradiol membrane action modulates ARH gamma-aminobutyric acid receptor-B (GABAB) activity. We tested the hypothesis that ARH GABAB receptors mediate estradiol-induced MOR activation and facilitation of sexual receptivity. Double-label immunohistochemistry revealed expression of GABAB receptors in NPY, ERα and POMC expressing ARH neurons. Approximately 70% of POMC neurons expressed GABAB receptors. Because estradiol initially activates an inhibitory circuit and maintains activation of this circuit, the effects of blocking GABAB receptors were evaluated before estradiol benzoate (EB) treatment and after at the time of lordosis testing. Bilateral infusions of the GABAB receptor antagonist, CGP52432, into the ARH prior to EB treatment of ovariectomized rats prevented estradiol-induced activation/internalization of MPN MOR, and the rats remained unreceptive. However, in EB-treated rats, bilateral CGP52432 infusions 30 min before behavior testing attenuated MOR internalization and facilitated lordosis. These results indicated that GABAB receptors were located within the lordosis-regulating ARH microcircuit and are necessary for activation and maintenance of the estradiol inhibition of lordosis behavior. Although GABAB receptors positively influence estradiol signaling, they negatively regulate lordosis behavior since GABAB activity maintains the estradiol-induced inhibition.
authors.affiliation: Biol. Sci., California State University, Long Beach, Long Beach, CA, USA. Kevin.sinchak@csulb.edu
authors.forename: Kevin
authors.initials: K
authors.lastname: Sinchak
authors.forename: Phoebe
authors.initials: P
authors.lastname: Dewing
authors.forename: Laura
authors.initials: L
authors.lastname: Ponce
authors.forename: Liliana
authors.initials: L
authors.lastname: Gomez
authors.forename: Amy
authors.initials: A
authors.lastname: Christensen
authors.forename: Max
authors.initials: M
authors.lastname: Berger
authors.forename: Paul
authors.initials: P
authors.lastname: Micevych
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D010052:Ovariectomy; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D058788:GABA-B Receptor Antagonists; D009478:Neuropeptide Y; D018080:Receptors, GABA-B; D017450:Receptors, Opioid, mu; D004958:Estradiol; D011333:Pro-Opiomelanocortin