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Agonist-induced μ-opioid receptor (MOPr) internalization has long been suggested to contribute directly to functional receptor desensitization and opioid tolerance. In contrast, recent evidence suggests that opioid receptor internalization could in fact reduce opioid tolerance in vivo, but the mechanisms that are responsible for the internalization-mediated protection against opioid tolerance are...
Rationale Despite numerous investigations, the mechanisms underlying the development of opioid tolerance are far from clear. However, several in vitro studies implicated a protective role of agonist-induced μ-opioid receptor endocytosis in the development of opioid tolerance. Moreover, we have recently demonstrated that the high-efficacy agonist etonitazene promotes rapid endocytosis of μ-opioid receptors,...
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