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Updated: Jun 13, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Development of morphine-induced tolerance and withdrawal: involvement of the clock gene mPer2

Stéphanie Perreau-Lenz1, Carles Sanchis-Segura, Fernando Leonardi-Essmann

  • 1Central Institute for Mental Health, Department of Psychopharmacology, CIMH, University of Heidelberg, Mannheim, Germany. stephanie.perreau-lenz@zi-mannheim.de

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
|May 4, 2010
PubMed

Insights

The clock gene mPer2 plays a role in morphine tolerance and withdrawal. Mutant mice lacking functional mPer2 exhibited reduced tolerance and milder withdrawal symptoms compared to wild-type mice.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Opioid tolerance and withdrawal are significant clinical challenges.
  • The circadian clock system, including the mPer2 gene, influences various physiological processes.
  • Understanding the genetic underpinnings of opioid dependence is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the specific role of the clock gene mPer2 in the development of morphine tolerance.
  • To assess the involvement of mPer2 in morphine-induced withdrawal symptoms.
  • To compare morphine dependence phenotypes between Per2(Brdm1) mutant mice and wild-type littermates.

Main Methods:

  • Utilized Per2(Brdm1) mutant mice and their wild-type (WT) littermates.
  • Assessed baseline gene expression related to morphine dependence.
  • Evaluated morphine-induced tolerance and precipitated withdrawal in both mouse groups.

Main Results:

  • No significant initial differences in relevant gene expression were observed between mutant and WT mice.
  • Per2(Brdm1) mutant mice demonstrated significantly reduced morphine tolerance compared to WT mice.
  • Attenuated withdrawal signs were observed in Per2(Brdm1) mutant mice relative to WT controls.

Conclusions:

  • The mPer2 gene is implicated in the mechanisms underlying morphine tolerance.
  • mPER2 activity is associated with the severity of morphine withdrawal symptoms.
  • Targeting the mPer2 pathway may offer a novel approach for managing opioid dependence.

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