Morphine-induced mu opioid receptor trafficking enhances reward yet prevents compulsive drug use.

ABSTRACT: Morphine, heroin and other commonly abused opioids induce little mu opioid receptor (MOR) trafficking compared to endogenous opioids. We utilized knock-in mice expressing a mutant recycling MOR (RMOR) that desensitizes and is internalized in response to morphine to show that facilitating MOR trafficking not only enhances morphine reward but, despite this, reduces the development of addiction-like behaviours. To demonstrate this, we developed a novel model of the transition from controlled to compulsive drug use that recapitulates many features of human addiction, including persistent drug seeking despite adverse consequences and a decreased preference for alternative rewards. These behaviours emerged spontaneously in wild-type but not RMOR mice, and their intensity predicted the reinstatem

SUBMITTER: Berger AC 

PROVIDER: S-EPMC3394511 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature