Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5.

ABSTRACT:

Background

The clinical benefits of opioid drugs are counteracted by the development of tolerance and addiction. We provide in vivo evidence for the involvement of G protein-coupled receptor kinases (GRKs) in opioid dependence in addition to their roles in agonist-selective mu-opioid receptor (MOR) phosphorylation.

Methods

In vivo MOR phosphorylation was examined by immunoprecipitation and nanoflow liquid chromatography-tandem mass spectrometry analysis. Using the hot-plate and conditioned place preference test, we investigated opioid-related antinociception and reward effects in mice lacking GRK3 or GRK5.

Results

Etonitazene and fentanyl stimulated the in vivo phosphorylation of multiple carboxyl-terminal phosphate acceptor sites, including threonine 370, serine 375,

SUBMITTER: Gluck L 

PROVIDER: S-EPMC4119866 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature