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We tested the hypothesis that gonadal steroids differentially modulate the ability ofOFQ<\/jats:styled-content>\/N<\/jats:styled-content>to inhibit these cells via presynaptic inhibition of transmitter release and postsynaptic activation ofG<\/jats:styled-content>protein\u2010gated, inwardly\u2010rectifyingK<\/jats:styled-content>+<\/jats:sup>(GIRK<\/jats:styled-content>)\u20101 channels. Whole\u2010cell patch clamp recordings were performed in hypothalamic slices prepared from ovariectomised rats. OFQ\/N (1\u00a0\u03bcm<\/jats:sc>) decreased the frequency of miniature excitatory postsynaptic currents (mEPSC<\/jats:styled-content>s) and miniature inhibitory postsynaptic currents (mIPSC<\/jats:styled-content>s), and also caused a robust outward current in the presence of tetrodotoxin, inARH<\/jats:styled-content>neurones from vehicle\u2010treated animals. A priming dose of oestradiol benzoate (EB; 2\u00a0\u03bcg) increased basal mEPSC<\/jats:styled-content>frequency, markedly diminished both theOFQ<\/jats:styled-content>\/N<\/jats:styled-content>\u2010induced decrease in mEPSC<\/jats:styled-content>frequency and the activation ofGIRK<\/jats:styled-content>\u20101 currents, and potentiated theOFQ<\/jats:styled-content>\/N<\/jats:styled-content>\u2010induced decrease in mIPSC<\/jats:styled-content>frequency. Steroid treatment regimens that facilitate sexual receptivity reinstate the basal mEPSC<\/jats:styled-content>frequency, theOFQ<\/jats:styled-content>\/N<\/jats:styled-content>\u2010induced decrease in mEPSC<\/jats:styled-content>frequency and the activation ofGIRK<\/jats:styled-content>\u20101 currents to levels observed in vehicle\u2010treated controls, and largely abolish the ability ofOFQ<\/jats:styled-content>\/N<\/jats:styled-content>to decrease mIPSC<\/jats:styled-content>frequency. These effects were observed in an appreciable population of identifiedPOMC<\/jats:styled-content>neurones, almost one\u2010half of which projected to the medial preoptic nucleus. Taken together, these data reveal that gonadal steroids influence the pleiotropic actions ofOFQ<\/jats:styled-content>\/N<\/jats:styled-content>onARH<\/jats:styled-content>neurones, includingPOMC<\/jats:styled-content>neurones, in a disparate manner. These temporal changes inOFQ<\/jats:styled-content>\/N<\/jats:styled-content>responsiveness further implicate this neuropeptide system as a critical mediator of the gonadal steroid regulation of reproductive behaviour.<\/jats:p>","DOI":"10.1111\/jne.12148","type":"journal-article","created":{"date-parts":[[2014,3,11]],"date-time":"2014-03-11T15:06:24Z","timestamp":1394550384000},"page":"329-340","source":"Crossref","is-referenced-by-count":13,"title":["Gonadal Steroids Differentially Modulate the Actions of OrphaninFQ<\/scp>\/Nociceptin at A Physiologically Relevant Circuit Controlling Female Sexual Receptivity"],"prefix":"10.1111","volume":"26","author":[{"given":"A.","family":"Borgquist","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences College of Osteopathic Medicine Western University of Health Sciences Pomona CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. 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