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

Amy Chang Berger1, Jennifer L Whistler

  • 1Neuroscience Program, University of California, San Francisco, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.

EMBO Molecular Medicine
|June 10, 2011
PubMed

Insights

Promoting mu opioid receptor (MOR) trafficking enhances morphine

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Commonly abused opioids like morphine cause limited mu opioid receptor (MOR) trafficking compared to endogenous opioids.
  • Understanding MOR trafficking is crucial for developing effective addiction treatments.

Purpose of the Study:

  • To investigate the role of MOR trafficking in morphine reward and addiction-like behaviors.
  • To determine if facilitating MOR trafficking can reduce addiction development while preserving rewarding effects.

Main Methods:

  • Utilized knock-in mice expressing a mutant recycling MOR (RMOR) that internalizes upon morphine exposure.
  • Developed a novel model to study the transition from controlled to compulsive drug use.
  • Compared spontaneous and induced addiction-like behaviors in wild-type and RMOR mice.

Main Results:

  • Facilitating MOR trafficking enhanced morphine reward.
  • Despite enhanced reward, RMOR mice showed reduced development of addiction-like behaviors.
  • Addiction-like behaviors in wild-type mice predicted relapse, independent of prior morphine intake.

Conclusions:

  • Addiction can be dissociated from reward and consumption.
  • Promoting agonist-induced MOR trafficking can simultaneously reduce morphine's addictiveness and enhance its desirable effects.
  • Targeting MOR trafficking offers a potential therapeutic strategy for opioid addiction.

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