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Research ArticleNEUROPHARMACOLOGY

Acute Antinociceptive Tolerance and Asymmetric Cross-Tolerance between Endomorphin-1 and Endomorphin-2 Given Intracerebroventricularly in the Mouse

Hsiang-en Wu, Kuei-chun Hung, Hirokazu Mizoguchi, James M. Fujimoto and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics December 2001, 299 (3) 1120-1125;
Hsiang-en Wu
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Kuei-chun Hung
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Hirokazu Mizoguchi
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James M. Fujimoto
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Leon F. Tseng
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Abstract

Development of tolerance in mice pretreated intracerebroventricularly with μ-opioid receptor agonist endomorphin-1, endomorphin-2, or [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) was compared between endomorphin-1- and endomorphin-2-induced antinociception with the tail-flick test. A 2-h pretreatment with endomorphin-1 (30 nmol) produced a 3-fold shift to the right in the dose-response curve for endomorphin-1. Similarly, a 1-h pretreatment with endomorphin-2 (70 nmol) caused a 3.9-fold shift to the right for endomorphin-2. In cross-tolerance experiments, pretreatment with endomorphin-2 (70 nmol) caused a 2.3-fold shift of the dose-response curve for endomorphin-1, whereas pretreatment with endomorphin-1 (30 nmol) caused no change of the endomorphin-2 dose-response curve. Thus, mice acutely tolerant to endomorphin-1 were not cross-tolerant to endomorphin-2, although mice made tolerant to endomorphin-2 were partially cross-tolerant to endomorphin-1; an asymmetric cross-tolerance occurred. Pretreatment with DAMGO 3 h before intracerebroventricular injection of endomorphin-1, endomorphin-2, or DAMGO attenuated markedly the antinociception induced by endomorphin-1 and DAMGO but not endomorphin-2. It is proposed that two separate subtypes of μ-opioid receptors are involved in antinociceptive effects induced by endomorphin-1 and endomorphin-2. One subtype of opioid μ-receptors is stimulated by DAMGO, endomorphin-1, and endomorphin-2, and another subtype of μ-opioidreceptors is stimulated solely by endomorphin-2.

Footnotes

  • This work was supported in part by Grant DA 03811 from the National Institutes of Health, National Institute on Drug Abuse (Principal Investigator: L.F.T.). A preliminary report of some of these results will be presented at the 31st Annual Meeting of the Society for Neuroscience, San Diego, CA, November 10–15, 2001.

  • Abbreviations:
    i.t.
    intrathecal
    DAMGO
    [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin
    ANOVA
    analysis of variance
    %MPE
    percent maximum possible effect
    • Received July 10, 2001.
    • Accepted September 6, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 3
1 Dec 2001
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Research ArticleNEUROPHARMACOLOGY

Acute Antinociceptive Tolerance and Asymmetric Cross-Tolerance between Endomorphin-1 and Endomorphin-2 Given Intracerebroventricularly in the Mouse

Hsiang-en Wu, Kuei-chun Hung, Hirokazu Mizoguchi, James M. Fujimoto and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1120-1125;

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Research ArticleNEUROPHARMACOLOGY

Acute Antinociceptive Tolerance and Asymmetric Cross-Tolerance between Endomorphin-1 and Endomorphin-2 Given Intracerebroventricularly in the Mouse

Hsiang-en Wu, Kuei-chun Hung, Hirokazu Mizoguchi, James M. Fujimoto and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1120-1125;
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