μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence

@article{Bohn2000OpioidRD,
  title={$\mu$-Opioid receptor desensitization by $\beta$-arrestin-2 determines morphine tolerance but not dependence},
  author={Laura M. Bohn and Raul R. Gainetdinov and Fang-Tsyr Lin and Robert J. Lefkowitz and Marc G. Caron},
  journal={Nature},
  year={2000},
  volume={408},
  pages={720-723}
}
Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G… 
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  • Biology
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  • 2005
TLDR
Modification of opioid receptor internalization by affecting the interaction between opioid receptors and beta-arrestins may be a therapeutic target for reducing opioid tolerance.
Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance
TLDR
It is shown that morphine tolerance was delayed in mice lacking vasopressin 1b receptors (V1bRs) or after administration of V1bR antagonist into the rostral ventromedial medulla, where transcripts for V 1bRs and μ-opioid receptors are co-localized.
Morphine-Induced μ-Opioid Receptor Desensitization
TLDR
It is shown that morphine does cause short-term desensitization, and whole-cell recordings from neurons in the locus ceruleus are used to measure the potassium current induced by morphine, suggesting that morphine, like other agonists, can initiate receptor desensitized to decrease signaling.
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