Opioid tolerance-in search of the holy grail

Cell. 2002 Mar 8;108(5):587-90. doi: 10.1016/s0092-8674(02)00666-9.


Tolerance, one of several behavioral adaptations to prolonged opioid treatment, has long been explained by desensitization of opioid receptor signaling and loss of surface receptors. However, recent evidence presents an alternative hypothesis, suggesting that receptor internalization could in fact reduce tolerance in vivo.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Tolerance / physiology*
  • Endocytosis / physiology
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / metabolism
  • Humans
  • Models, Biological
  • Narcotics / therapeutic use*
  • Receptors, Opioid / metabolism
  • Signal Transduction / physiology


  • Narcotics
  • Receptors, Opioid
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-