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Gonadal Steroids Differentially Modulate the Actions of Orphanin FQ /Nociceptin at A Physiologically Relevant Circuit Controlling Female Sexual Receptivity
Author(s) -
Borgquist A.,
Rivas V. M.,
Kachani M.,
Sinchak K.,
Wagner E. J.
Publication year - 2014
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12148
Subject(s) - nociceptin receptor , endocrinology , medicine , receptivity , biology , opioid peptide , receptor , opioid
Orphanin FQ /nociceptin ( OFQ / N ) inhibits the activity of pro‐opiomelanocortin ( POMC ) neurones located in the hypothalamic arcuate nucleus ( ARH ) that regulate female sexual behaviour and energy balance. We tested the hypothesis that gonadal steroids differentially modulate the ability of OFQ / N to inhibit these cells via presynaptic inhibition of transmitter release and postsynaptic activation of G protein‐gated, inwardly‐rectifying K + ( GIRK )‐1 channels. Whole‐cell patch clamp recordings were performed in hypothalamic slices prepared from ovariectomised rats. OFQ/N (1 μ m ) decreased the frequency of miniature excitatory postsynaptic currents (m EPSC s) and miniature inhibitory postsynaptic currents (m IPSC s), and also caused a robust outward current in the presence of tetrodotoxin, in ARH neurones from vehicle‐treated animals. A priming dose of oestradiol benzoate (EB; 2 μg) increased basal m EPSC frequency, markedly diminished both the OFQ / N ‐induced decrease in m EPSC frequency and the activation of GIRK ‐1 currents, and potentiated the OFQ / N ‐induced decrease in m IPSC frequency. Steroid treatment regimens that facilitate sexual receptivity reinstate the basal m EPSC frequency, the OFQ / N ‐induced decrease in m EPSC frequency and the activation of GIRK ‐1 currents to levels observed in vehicle‐treated controls, and largely abolish the ability of OFQ / N to decrease m IPSC frequency. These effects were observed in an appreciable population of identified POMC neurones, almost one‐half of which projected to the medial preoptic nucleus. Taken together, these data reveal that gonadal steroids influence the pleiotropic actions of OFQ / N on ARH neurones, including POMC neurones, in a disparate manner. These temporal changes in OFQ / N responsiveness further implicate this neuropeptide system as a critical mediator of the gonadal steroid regulation of reproductive behaviour.