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Research ArticleNEUROPHARMACOLOGY

Acute Opioid Pretreatment Potentiates Naltrexone-Induced Drinking Suppression in Water-Deprived Rats

David A. White and Stephen G. Holtzman
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 156-164;
David A. White
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Stephen G. Holtzman
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Abstract

Pretreatment with morphine-like agonists potentiates the behavioral effects of opioid antagonists, possibly reflecting a state of acute physical dependence. Several studies have used operant behavior to quantify these effects. However, little research has been done using unconditioned behavior. One objective of this study was to determine whether opioid agonist pretreatment (e.g., morphine, fentanyl, and meperidine) potentiated naltrexone-induced suppression of water consumption following deprivation. Another objective was to determine whether the agonist pretreatment interval was functionally related to efficacy for the manifestation of acute dependence. Finally, we compared temporally the effects of the three agonists. Adult male Sprague-Dawley rats were water deprived for 18, 20, or 22 h and given an injection (s.c.) of an agonist or saline. After 1.75, 3.75, or 5.75 h, animals received a single dose (s.c.) of naltrexone (0.01–30 mg/kg) or saline. Fifteen minutes later, subjects had access to water for 30 min. A time course of antinociception was constructed after agonist administration, using the tail-flick procedure. All three agonists dose dependently potentiated naltrexone-induced drinking suppression, decreasing the ED50 of naltrexone by as much as 150-fold. There was no clear relationship between agonist efficacy and pretreatment interval. Sensitization to naltrexone was seen up to 6 h after agonist administration, occurring in the apparent absence of an antinociceptive effect. These data extend the range of behavioral effects of opioid antagonists potentiated by opioid agonist pretreatment to suppression of drinking and show that such potentiation can occur in the absence of a prototypical agonist effect.

Footnotes

  • This research was supported by National Institutes of Health Grants DA00541 and K05 DA00008.

  • Abbreviations:
    ANOVA
    analysis of variance
    % MPE
    percentage maximum possible effect
    AUC
    area under the curve
    FEN
    fentanyl
    MEP
    meperidine
    MOR
    morphine
    Pre-tx
    pretreatment
    SAL
    saline
    • Received January 29, 2001.
    • Accepted March 27, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleNEUROPHARMACOLOGY

Acute Opioid Pretreatment Potentiates Naltrexone-Induced Drinking Suppression in Water-Deprived Rats

David A. White and Stephen G. Holtzman
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 156-164;

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Research ArticleNEUROPHARMACOLOGY

Acute Opioid Pretreatment Potentiates Naltrexone-Induced Drinking Suppression in Water-Deprived Rats

David A. White and Stephen G. Holtzman
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 156-164;
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