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Adrenal steroids indirectly modulate morphine and beta-endorphin effects

J W Holaday, P Y Law, H H Loh

    The Journal of Pharmacology and Experimental Therapeutics
    |February 1, 1979
    PubMed
    Summary

    Adrenalectomy sensitizes animals to opiates like morphine by decreasing their metabolism. Dexamethasone reverses this effect by inducing proteins involved in opiate metabolism, suggesting a corticosteroid-endorphin interplay.

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    Area of Science:

    • Pharmacology
    • Endocrinology
    • Neuroscience

    Background:

    • Adrenalectomy alters animal responses to opiates.
    • Glucocorticoids like dexamethasone may influence opiate effects.
    • The role of protein synthesis in these interactions is unclear.

    Purpose of the Study:

    • To investigate the impact of adrenalectomy on morphine and beta-endorphin effects.
    • To determine the role of dexamethasone and protein synthesis in modulating opiate sensitivity.
    • To explore the interaction between corticosteroids and endogenous opiates.

    Main Methods:

    • Comparing pharmacological effects of morphine and beta-endorphin in adrenalectomized and sham-control animals.
    • Assessing the impact of dexamethasone and cycloheximide pretreatment on opiate responses.

    Related Experiment Videos

  • Measuring tritium counts in blood and brain after parenteral morphine administration.
  • Evaluating the effect of SKF 525-A on opiate potency.

    • Main Results:

    • Adrenalectomy sensitized rats and mice to parenteral opiates.
    • Dexamethasone pretreatment abolished this sensitization, an effect blocked by cycloheximide.
    • Adrenalectomized mice showed higher tritium levels in blood and brain after morphine, also blocked by dexamethasone.
    • SKF 525-A altered opiate potency, suggesting involvement of metabolic enzymes.

    Conclusions:

    • Adrenalectomy decreases morphine metabolism, enhancing its potency via increased bioavailability.
    • Dexamethasone's reversal effect depends on de novo protein synthesis in the opiate-metabolizing system.
    • A physiological interplay between endorphins and corticosteroids is suggested by dexamethasone's effects on beta-endorphin.