Estrogen receptor-α is required for estrogen-induced μ-opioid receptor internalization

Paul E. Micevych, Emilie F. Rissman, Jan Åke Gustafsson, Kevin Sinchak

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Endogenous opioid circuits are pivotal for the regulation of sexual receptivity. Treatment of mice with morphine, a preferential μ-opioid receptor (MOR) agonist, severely attenuates lordosis. Estrogen induces internalization of MOR in cell groups of the limbic-hypothalamic lordosis-regulating circuit. Because rapid MOR internalization is mediated by estrogen release of endogenous opioid peptides, internalization has been used as a neurochemical signature of estrogen action in the central nervous system. Together these results indicate that estrogen induces a MOR mediated inhibition of sexual receptivity. To determine which estrogen receptor, estrogen receptor-α (ERα) or estrogen receptor-β (ERβ), mediates MOR internalization, ERα knockout (ERαKO), ERβ knockout (ERβKO) and wild-type (WT) mice were used in the present study. WT, ERαKO and ERβKO mice had similar MOR distributions in the limbic-hypothalamic lordosis-regulating circuit. Estrogen treatment internalized MOR in the medial preoptic nucleus of ovariectomized WT and ERβKO, but not ERαKO mice. Treatment of ERαKO mice with the selective endogenous MOR ligand, endomorphin-1, induced levels of MOR internalization similar to WT mice suggesting that MOR in ERαKO mice could be activated and were probably functional. The results of the present experiments indicate that ERα is required for estrogen-induced MOR internalization and suggest that ERα can mediate rapid actions of estrogen.

Original languageEnglish (US)
Pages (from-to)802-810
Number of pages9
JournalJournal of Neuroscience Research
Issue number6
StatePublished - Mar 15 2003


  • Endomorphin-1
  • ERαko
  • ERβko
  • Female reproductive behavior
  • Internalization of mu-opioid receptor
  • Lordosis
  • Medial amygdala
  • Medial preoptic nucleus
  • Morphine

ASJC Scopus subject areas

  • Neuroscience(all)


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