Immunohistochemical evidence of down-regulation of μ-opioid receptor after chronic PL-017 in rats

Pao Luh Tao, Kuang Fen Han, Shwun De Wang, Wei Ming Lue, Robert Elde, Ping Yee Law, Horace H. Loh

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21 Scopus citations


In a previous study, μ-opioid receptor binding was decreased by chronic treatment of rats with a μ-opioid receptor-selective agonist [CH3Phe3, D- Pro4]morphiceptin (PL-017) [Tao, P.L., Lee, H.Y., Chang, L.R., Loh, H.H., 1990. Decrease in μ-opioid receptor binding capacity in rat brain after chronic PL-017 treatment. Brain Res. 526, 270-275]. However, there was a lack of correlation between the time course of receptor down-regulation and the loss of pharmacological effects of the drug. In the current study, we used immunohistochemistry to reinvestigate this issue. Male Sprague-Dawley rats were chronically treated with PL-017 i.c.v. for 1, 3 or 5 days, using an escalating dosage paradigm (0.75-6.0 μg), which resulted in a 1.4 to 32- fold increase in the AD50. Rat brains were removed, frozen, coronally sectioned (14 μm) and processed for μ-, δ- or κ-opioid receptor immunohistochemistry by the avidin-biotin complex (ABC) method. Significant decreases in OP3 immunodensity were found in many brain regions which are enriched with OP3 after chronic treatment of PL-017, Time-dependent decreases in OP3 were detected and reached a plateau around 3 days of PL-017 treatment. No significant change in OP1 or OP2 immunodensity after chronic treatment with PL-017 was found. Our conclusion is that chronic treatment with PL-017 of rats selectively down-regulates μ-opioid receptors in the brain. This may be an important mechanism for PL-017 tolerance.

Original languageEnglish (US)
Pages (from-to)137-142
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Mar 5 1998

Bibliographical note

Funding Information:
This study was supported by a grant from the National Science Council (NSC 85-2331-B-016-113) and by a Grant from the National Health Research Institutes (DOH-85-HR-402), Taipei, Taiwan, Republic of China.


  • Antinociception
  • Down- regulation
  • Immunohistochemistry
  • Opioid receptor
  • PL-017
  • Tolerance


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