Nature of seasonal variation in development of acute tolerance to morphine.

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.