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Related Experiment Videos

Interactions between narcotic agonists, partial agonists and antagonists evaluated by schedule-controlled behavior.

R A Harris

    The Journal of Pharmacology and Experimental Therapeutics
    |June 1, 1980
    PubMed
    Summary

    Narcotic antagonists like naltrexone and naloxone differentially block the effects of various opioid drugs in rats. This differential antagonism supports distinct mu, kappa, and sigma opioid receptors.

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    Area of Science:

    • Pharmacology
    • Neuroscience
    • Behavioral Science

    Background:

    • Opioid drugs exert their effects through interactions with specific receptors in the central nervous system.
    • Understanding these interactions is crucial for developing targeted analgesics and addiction treatments.
    • Narcotic antagonists are key tools for probing opioid receptor pharmacology.

    Purpose of the Study:

    • To investigate the differential effects of various opioid agonists and their interactions with narcotic antagonists (naloxone and naltrexone).
    • To classify opioid drugs based on their response to antagonism, providing evidence for distinct receptor subtypes.
    • To test the validity of the proposed mu, kappa, and sigma opioid receptor hypothesis.

    Main Methods:

    • Rats were trained to respond on a fixed-interval (5-min) schedule for food presentation.

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  • The effects of morphine, butorphanol, cyclazocine, ketocyclazocine, ethylketocyclazocine, and SKF-10,047 were assessed alone and in combination with naloxone or naltrexone.
  • Dose-response curves were analyzed to determine the degree of antagonism.

    • Main Results:

    • All tested opioid agonists, except naloxone and naltrexone, dose-dependently decreased responding.
    • Naltrexone markedly antagonized morphine's effects, while SKF-10,047 and high-dose cyclazocine were not antagonized.
    • Butorphanol, ketocyclazocine, ethylketocyclazocine, and low-dose cyclazocine were antagonized but required higher antagonist doses than morphine.

    Conclusions:

    • The differential antagonism by naloxone and naltrexone supports the classification of opioid drugs into three groups based on their receptor interactions.
    • Findings are consistent with the existence of distinct mu (morphine), kappa (ketocyclazocine, ethylketocyclazocine), and sigma (SKF-10,047) opioid receptors.
    • This study provides pharmacological evidence supporting the multi-receptor model for opioid action.