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mu Opioid receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality

H H Loh1, H C Liu, A Cavalli

  • 1Dept. of Pharmacology, University of Minnesota Medical School, 3-249 Millard Hall, 435 Delaware St. S.E., Minneapolis, MN 55455, USA. lohxx001@maroon.tc.umn.edu

Brain Research. Molecular Brain Research
|May 16, 1998
PubMed

Insights

Mice lacking the mu opioid receptor gene (MOR) showed significantly reduced pain relief from morphine and its metabolites. This indicates the mu receptor is crucial for morphine

Area of Science:

  • Pharmacology
  • Neuroscience
  • Genetics

Background:

  • The mu opioid receptor (MOR) is a key target for pain relief.
  • Understanding MOR's role is vital for developing effective analgesics.

Purpose of the Study:

  • To investigate the specific role of the mu opioid receptor in mediating the effects of morphine and related compounds.
  • To determine if MOR is essential for morphine-induced analgesia and lethality.

Main Methods:

  • Gene targeting was used to create MOR-knockout mice.
  • Analgesic and lethal effects of various opioid ligands were tested in these mice.

Main Results:

  • MOR-knockout mice exhibited drastically reduced analgesic effects from morphine, morphine-6-glucuronide (M-6-G), morphine-6-ethereal sulfate (M-6-S), and endomorphin-2.
  • Morphine-induced lethality was also significantly reduced in MOR-knockout mice.
  • The effects of DPDPE and U50488 were unchanged, suggesting a specific role for MOR.

Conclusions:

  • The mu opioid receptor mediates the analgesic effects of mu-specific opioid ligands.
  • Acute morphine lethality is also mediated by the mu receptor.

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