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[Motility effects of morphine in morphine-tolerant mice by the DAF method]
Abstract:
Effects of repeated administration of morphine on ambulatory activity were studied in mice treated with morphine-admixed food. The ambulatory activity was determined by the tilting cage method. Morphine injection (10 mg/kg s.c.) was repeated at 3-4 day intervals. The ambulatory activity was enhanced progressively when morphine was repeatedly given to mice. However, the enhancing effect was not observed in mice treated with morphine-admixed food (1 mg/g food). These results suggested that the reverse tolerance to morphine did not develop under the condition of exposure to morphine by DAF (drug-admixed food) method. In case of treatment with morphine-admixed food of increasing concentration (1,2 and 3 mg/g food), the ambulatory activity of morphine was decreased. According to the studies done so far, tolerance development to the stimulant effects was not observed. This study demonstrates that the tolerance develops to the stimulant effects of morphine on the schedule of treatment with morphine of increasing doses by the DAF method.
Insights
Repeated morphine injections increase ambulatory activity in mice. However, tolerance to morphine's stimulant effects develops when using the drug-admixed food method with increasing doses.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Context:
- Opioid analgesics like morphine are widely used for pain management.
- Understanding the development of tolerance to morphine's effects is crucial for clinical applications.
- Previous research indicated a lack of tolerance to morphine's stimulant effects via oral administration.
Purpose:
- To investigate the effects of repeated morphine administration on ambulatory activity in mice.
- To determine if tolerance develops to morphine's stimulant effects using the drug-admixed food (DAF) method.
- To compare tolerance development between subcutaneous morphine injections and DAF administration.
Summary:
- Repeated subcutaneous morphine injections (10 mg/kg) progressively enhanced ambulatory activity in mice.
- Mice treated with a constant dose of morphine-admixed food (1 mg/g) did not show enhanced activity, suggesting no reverse tolerance.
- However, when mice were treated with gradually increasing concentrations of morphine-admixed food (1, 2, and 3 mg/g), tolerance to the stimulant effects of morphine did develop.
Impact:
- This study demonstrates that tolerance to morphine's stimulant effects can be achieved using the drug-admixed food method with escalating doses.
- Findings suggest that the route and method of drug administration significantly influence tolerance development.
- This research provides insights into novel strategies for managing opioid tolerance.