μ opioid receptor knockout in mice: Effects on ligand-induced analgesia and morphine lethality

Horace H Loh, Hsien Ching Liu, Antonella Cavalli, Wanling Yang, Yuh Fung Chen, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

286 Scopus citations

Abstract

The μ opioid receptor gene (MOR) was mutated in mice by a gene targeting procedure. In these MOR-knockout mice, the analgesic effects of morphine, its major metabolites, morphine-6-glucuronide (M-6-G) and morphine-6-ethereal sulfate (M-6-S), and endomorphin-2, as well as morphine-induced lethality, were drastically reduced, whereas the effects of DPDPE and U50488 remained unchanged. It is concluded that analgesic effects of μ-specific opioid ligands and acute morphine lethality are mediated by the μ receptor.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalMolecular Brain Research
Volume54
Issue number2
DOIs
StatePublished - Mar 1 1998

Bibliographical note

Funding Information:
We thank Dr. D.W. Melton for granting permission to use the HM1 ES cells, professor Lan Bo Chan for his generous help in many essential parts of this work, Drs. Jim Fujimoto and Pasternak for providing samples of morphine metabolites and Dr. Jim Zadina for providing a sample of endomorphin. This work was supported by NIH grants DA00564, DA01583, DA05695, K05-DA70554, and the F&A Stark Fund of the Minnesota Medical Foundation to HHL.

Keywords

  • Gene-targeting
  • Morphine analgesia
  • Morphine lethality
  • μ opioid receptor

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