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Related Experiment Videos

A new ingestion method for long-term morphine intoxication in rat.

J Zeuchner, L Rosengren, A Wronski

    Pharmacology, Biochemistry, and Behavior
    |September 1, 1982
    PubMed
    Summary

    Researchers developed a novel method for long-term morphine intoxication in rats, administering it via diet to prevent weight loss. This technique ensures standardized, safe, and cost-effective morphine administration for extensive studies.

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    Area of Science:

    • Pharmacology
    • Neuroscience
    • Animal Models

    Background:

    • Conventional methods for inducing long-term morphine intoxication in rats often lead to nutritional imbalance and significant body weight loss.
    • These adverse effects complicate research outcomes and animal welfare during prolonged morphine administration studies.

    Purpose of the Study:

    • To develop and validate a new, improved method for achieving long-term morphine intoxication in rats.
    • To overcome the limitations of traditional methods, specifically addressing nutritional deficits and weight loss.
    • To establish a standardized, cost-effective, and safe protocol for chronic morphine administration in preclinical research.

    Main Methods:

    • Morphine was administered orally within a nutritionally complete diet to rats.

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  • Pair-feeding techniques were employed to control for variations in food intake between intoxicated and control groups.
  • The method was validated by testing various intoxication conditions, including different initial, incremental, and final morphine doses.
  • Dependence was assessed through withdrawal signs and antagonist challenges.
  • Plasma morphine levels and diet preference were also evaluated.

    • Main Results:

    • A regimen starting at 25 mg/kg and escalating to 340 mg/kg over 8 days induced morphine dependence.
    • Rats tolerated final doses up to 715 mg/kg within 13 days without reduced food intake.
    • Higher initial doses (340 or 715 mg/kg) resulted in impaired weight gain and diet consumption.
    • Plasma morphine concentrations reached 3 µg/ml serum at a dose of 340 mg/kg.
    • Rats exhibited a preference for the morphine-containing diet over the control diet.

    Conclusions:

    • The novel dietary method provides a simple, time-saving, and inexpensive approach for long-term, standardized morphine intoxication in rats.
    • This technique effectively mitigates nutritional imbalance and weight loss associated with conventional methods.
    • The protocol allows for the study of chronic morphine effects in numerous animals over extended periods without significant adverse health outcomes or mortality.