Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization

Li He, Jamie Fong, Mark Von Zastrow, Jennifer Whistler

Research output: Contribution to journalArticlepeer-review

282 Scopus citations


The utility of morphine for the treatment of chronic pain is hindered by the development of tolerance to the analgesic effects of the drug. Morphine is unique among opiates in its ability to activate the mu opioid receptor (MOR) without promoting its desensitization and endocytosis. Here we demonstrate that [D-Ala2-MePhe4-Gly5-ol] enkephalin (DAMGO) can facilitate the ability of morphine to stimulate MOR endocytosis. As a consequence, rats treated chronically with both drugs show reduced analgesic tolerance compared to rats treated with morphine alone. These results demonstrate that endocytosis of the MOR can reduce the development of tolerance, and hence suggest an approach for the development of opiate analogs with enhanced efficacy for the treatment of chronic pain.

Original languageEnglish (US)
Pages (from-to)271-282
Number of pages12
Issue number2
StatePublished - Jan 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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