Tolerance to morphine analgesia from brief exposure to a palatable solution

The onset of tolerance to morphine analgesia was studied in 34 female Wistar rats immediately after they drank a dextrose-saccharin cocktail or tap water for 6 or 24 hours. Tail flick tests conducted at the end of the drinking period showed no analgesia in cocktail or water groups. Morphine (3.5 mg/kg) was then injected subcutaneously, and after 20 min another series of tail flick tests was conducted. Morphine produced strong analgesia in rats that drank water, but only partial analgesia in rats that drank the cocktail. This reduction in morphine analgesia did not differ in comparisons between 6-hour and 24-hour cocktail groups. The results were interpreted as indicating that ingestion of the cocktail produced tolerance for morphine in the test of analgesia, and that such factors as novelty of flavor stimulation or stress from repeated testing were unlikely to yield the attenuation of analgesia that was observed. It was concluded that processes that produce tolerance become active in less than 6 hours.