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Methadone induced physical dependence in the rat.

G S Ling, N S Tappe, C E Inturrisi

    Life Sciences
    |February 13, 1984
    PubMed
    Summary

    Chronic methadone infusion in rats induced physical dependence, manifesting a withdrawal syndrome similar to morphine. Naloxone administration precipitated these distinct behavioral and physiological signs in dependent rats.

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    Area of Science:

    • Pharmacology
    • Neuroscience
    • Addiction Research

    Background:

    • The morphine withdrawal syndrome is well-documented in rats.
    • However, a comparable syndrome following chronic methadone treatment has not been clearly demonstrated.
    • Understanding opioid withdrawal is crucial for addiction treatment and management.

    Purpose of the Study:

    • To investigate the development of physical dependence and withdrawal signs following chronic intravenous methadone administration in rats.
    • To compare the withdrawal syndrome induced by methadone with that of morphine.
    • To characterize the behavioral and physiological effects of naloxone-precipitated withdrawal after methadone or morphine treatment.

    Main Methods:

    • Rats received continuous intravenous infusions of methadone, morphine, or saline for 72 hours.
    • Naloxone (4 mg/kg) was administered subcutaneously after the infusion period to precipitate withdrawal.
    • Behavioral signs (e.g., wet dog shakes, escape attempts) and physiological signs (e.g., diarrhea, tachypnea) were recorded and quantified.

    Main Results:

    • Cessation of methadone or morphine treatment, followed by naloxone, resulted in a graded series of withdrawal signs.
    • Observed signs included wet dog shakes, escape attempts, self-stimulation, body weight loss, diarrhea, ear blanching, exophthalmos, ptosis, tachypnea, and teeth chattering.
    • Saline-treated rats did not exhibit these withdrawal phenomena.

    Conclusions:

    • Continuous intravenous methadone administration in rats produces physical dependence.
    • The precipitated withdrawal syndrome is characterized by signs similar to those observed in morphine withdrawal.
    • These findings demonstrate a morphine-like withdrawal syndrome following chronic methadone administration in rats, highlighting its potential for inducing physical dependence.

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