Functional dissociation of μ opioid receptor signaling and endocytosis: Implications for the biology of opiate tolerance and addiction

Jennifer Whistler, Huai Hu Chuang, Peter Chu, Lily Y. Jan, Mark Von Zastrow

Research output: Contribution to journalArticle

356 Scopus citations

Abstract

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the μ opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitization and endocytosis of receptors. Here, we demonstrate that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties. Moreover, this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of our understanding of the role of receptor endocytosis in the biology of opiate drug action and addiction.

Original languageEnglish (US)
Pages (from-to)737-746
Number of pages10
JournalNeuron
Volume23
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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