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Nature of seasonal variation in development of acute tolerance to morphine
Abstract:
Morphine inhibits contractions of coaxially stimulated guinea pig ileum. Acute tolerance to this effect occurs on continuous perfusion with morphine for 1.5 h. This is associated with an increase in the sensitivity of the tissue to acetylcholine. Acute tolerance does not always develop in spite of identical treatment, but shows a distinct seasonal incidence. It is significantly higher in the summer (May--Nov.) than winter (Dec.--April). This seasonal variation in development of tolerance does not appear to be related to changes in diet, environmental light or temperature, or to the sensitivity of the ileum to morphine. In the winter, the acetylcholine release from stimulated ilea is lower than in the summer. In addition to inhibiting acetylcholine release, morphine also has a non-specific blocking effect in the winter. This postjunctional effect could prevent the development of supersensitivity to acetylcholine during continuous morphine treatment so that acute tolerance cannot occur.
Insights
Acute tolerance to morphine
Area of Science:
- Pharmacology
- Physiology
Background:
- Morphine inhibits guinea pig ileum contractions.
- Acute tolerance to morphine can develop with continuous exposure.
- Tolerance is linked to changes in acetylcholine sensitivity.
Purpose of the Study:
- Investigate the development of acute morphine tolerance in guinea pig ileum.
- Explore the seasonal variations in tolerance development.
- Determine the underlying mechanisms for seasonal differences.
Main Methods:
- Continuous perfusion of guinea pig ileum with morphine.
- Measurement of ileum contractions and acetylcholine sensitivity.
- Comparison of summer and winter tolerance incidence.
Main Results:
- Acute tolerance to morphine's inhibitory effect was observed.
- Tolerance development showed significant seasonal variation, higher in summer.
- Acetylcholine release was lower in winter; morphine had additional blocking effects.
Conclusions:
- Seasonal variations in guinea pig ileum response to morphine exist.
- Winter conditions may involve non-specific postjunctional blocking, preventing tolerance.
- Further research is needed to elucidate the precise mechanisms of seasonal tolerance.