Regulation of μ-opioid receptors, G-protein-coupled receptor kinases and β-arrestin 2 in the rat brain after chronic opioid receptor antagonism

被引：43

作者：

Díaz, A ^{[1
]}

Pazos, A ^{[1
]}

Flórez, J ^{[1
]}

Ayesta, FJ ^{[1
]}

Santana, V ^{[1
]}

Hurlé, MA ^{[1
]}

机构：

[1] Univ Cantabria, Dept Physiol & Pharmacol, Sch Med, E-39011 Santander, Spain

来源：

NEUROSCIENCE | 2002年 / 112卷 / 02期

关键词：

autoradiography; analgesia; breathing; naloxone; naltrexone;

D O I：

10.1016/S0306-4522(02)00073-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The aim of this study was to analyse the biochemical and behavioural consequences of chronic treatment with opioid receptor antagonists in rats. We have evaluated the respiratory depressant and antinociceptive effects of the Ropioid agonist sufentanil, the density of brain mu-opioid receptors, and the expression of G-protein-coupled receptor kinases and beta-arrestin 2 in cerebral cortex and striaturn, following sustained opioid receptor blockade. Our results demonstrate that 24 h after interruption of 7 days chronic infusion of naltrexone (120 mug/h), the respiratory depressant potency of the mu-opioid receptor agonist sufentanil was increased to a similar extent as the antinociceptive potency (about three-fold). This was accompanied by g-opioid receptor up-regulation in several areas of the rat brain associated with opioid control of pain perception and breathing. Moreover, chronic treatment with either naltrexone (120 mug/h) or naloxone (120 mug/h) caused significant increases in the expression levels of G-protein-coupled receptor kinases types 2, 3, and 6, and of beta-arrestin 2 in brain cortex and striatum. Together our data suggest an increased constitutive receptor activity secondary to mu-opioid receptor up-regulation following chronic antagonist treatment. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.

引用

页码：345 / 353

页数：9

共 43 条

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