Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1

Nat Neurosci. 1999 Feb;2(2):151-6. doi: 10.1038/5706.


Morphine produces analgesia by activating mu opioid receptors encoded by the MOR-1 gene. Although morphine-6 beta-glucuronide (M6G), heroin and 6-acetylmorphine also are considered mu opioids, recent evidence suggests that they act through a distinct receptor mechanism. We examined this question in knockout mice containing disruptions of either the first or second coding exon of MOR-1. Mice homozygous for either MOR-1 mutation were insensitive to morphine. Heroin, 6-acetylmorphine and M6G still elicited analgesia in the exon-1 MOR-1 mutant, which also showed specific M6G binding, whereas M6G and 6-acetylmorphine were inactive in the exon-2 MOR-1 mutant. These results provide genetic evidence for a unique receptor site for M6G and heroin analgesia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Drug Resistance / genetics
  • Exons / genetics*
  • Heroin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Mice, Knockout / physiology
  • Morphine Derivatives / pharmacology*
  • Receptors, Opioid, mu / genetics*
  • Transcription, Genetic / physiology


  • Analgesics, Opioid
  • Morphine Derivatives
  • Receptors, Opioid, mu
  • morphine-6-glucuronide
  • Heroin
  • 6-O-monoacetylmorphine