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Updated: Oct 16, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Immunohistochemical study of opioid receptors after chronic morphine treatment in rats

P L Tao1, H S Niu, W M Lue

  • 1Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.

Proceedings of the National Science Council, Republic of China. Part B, Life Sciences
|April 29, 2000
PubMed

Insights

Down-regulation of opioid receptors is not a key factor in developing morphine tolerance. This study found no significant decrease in mu-opioid receptor or delta-opioid receptor levels after chronic morphine treatment.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Morphine tolerance is a complex phenomenon.
  • Previous studies suggested opioid receptor down-regulation as a potential mechanism.

Purpose of the Study:

  • To investigate the role of opioid receptor down-regulation in morphine tolerance using immunohistochemistry.
  • To re-evaluate previous findings on receptor binding methods.

Main Methods:

  • Chronic morphine administration to Sprague-Dawley rats over 2, 4, or 6 days with escalating doses.
  • Immunohistochemistry (Avidin-Biotin Complex method) to assess mu-opioid receptor (MOR) and delta-opioid receptor (DOR) immunodensity in rat brains.
  • Quantification of receptor levels in various brain regions.

Main Results:

  • Chronic morphine treatment led to a 1.8 to 4.0-fold increase in AD50, indicating tolerance.
  • No significant decrease in MOR immunodensity was observed in most brain regions.
  • No significant changes in DOR immunodensity were detected after chronic morphine treatment.

Conclusions:

  • Opioid receptor down-regulation is unlikely to be a major mechanism contributing to morphine tolerance.
  • Immunohistochemistry provides further evidence against receptor down-regulation as a primary cause of tolerance.

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