EARLY ONSET OF REDUCED MORPHINE ANALGESIA BY INGESTION OF SWEET SOLUTIONS

Morphine analgesia can be reduced by prior exposure to food and flavored fluids. The early onset of reduced morphine-induced analgesia (RMA) was studied in 82 male Wistar rats after allowing them access to either a dextrose-saccharin solution or unflavored tap water for 6 or 3 h (Experiment 1, n = 40) or for 3 h, 90, or 45 min (Experiment 2, n = 42). Morphine (4 mg/kg) was injected subcutaneously at the end of the drinking period, and after 25 min a series of tail flick tests was conducted. Morphine produced strong analgesia in all rats that drank unflavored tap water; however, in rats that drank the flavored solution, the analgesic effect of morphine was significantly attenuated following exposures of 6 or 3 h, but not following exposures of 90 or 45 min. Similar quantities of flavored fluid were consumed by groups at all exposure durations; thus, RMA was determined by duration of exposure and not amount consumed. No analgesia attributable to flavor consumption per se was observed. The results suggest that RMA is mediated by endogenous opioid activity in the gustatory and analgesic systems by a mechanism akin to tolerance that requires about 3 h to operate.