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Acute and chronic morphine administration in swine
J M Risdahl1, C Chao, M P Murtaugh
1Department of Clinical and Population Sciences, University of Minnesota, St. Paul 55108.
Pharmacology, Biochemistry, and Behavior
|November 1, 1992
Summary
Swine reliably model morphine effects, showing tolerance to pain relief and weight gain with constant drug levels. Dependence was confirmed by naloxone-induced withdrawal symptoms.
Area of Science:
- Pharmacology
- Veterinary Medicine
- Animal Models
Background:
- Morphine is a widely used analgesic with complex physiological effects.
- Understanding its pharmacokinetics and pharmacodynamics in animal models is crucial for research.
- Domestic swine offer a large animal model for preclinical studies.
Purpose of the Study:
- To investigate the functional responses to acute and chronic morphine administration in swine.
- To correlate these responses with morphine's pharmacokinetic profiles.
- To establish swine as a reliable model for studying opiate-like compounds.
Main Methods:
- Monitoring serum morphine levels, nociception, locomotor activity, respiration, temperature, and weight.
- Utilizing a novel thermal stimulating device for nociception assessment.
- Administering morphine sulfate (IV and SC) and delayed-release morphine alkaloid (SC).
- Inducing withdrawal symptoms with naloxone to assess dependence.
Main Results:
- Morphine sulfate had a ~1-hour half-life; delayed-release morphine alkaloid had a ~28-hour half-life.
- Antinociception correlated with declining blood morphine levels.
- Tolerance developed to antinociception and weight gain, despite stable morphine levels over 21 days.
- Naloxone precipitated a consistent abstinence syndrome, confirming morphine dependence.
Conclusions:
- Swine exhibit predictable pharmacokinetic and functional responses to morphine.
- Tolerance and dependence develop in swine models, mimicking human responses.
- Domestic swine are a suitable and reliable model for studying morphine and related compounds.