[Assessment of morphine-type physical dependence liability in mice using the drug-admixed food method]

Physical dependence on morphine-type drugs (morphine, codeine and pethidine) in mice were examined by the drug-admixed food method. Mice were treated with drug-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. Morphine- and codeine-treated mice showed withdrawal signs when they were given naloxone (5 mg/kg, s.c.), while pethidine-treated mice did not show the withdrawal signs. However, mice treated with pethidine-admixed food (1-6 mg/g food) for 28 days showed naloxone precipitated withdrawal signs. Thus, the data obtained with mice indicate that pethidine produces a weak physical dependence. On the other hand, codeine (40 mg/kg, s.c.) and pethidine (100 mg/kg, s.c.) administration suppressed the abrupt withdrawal signs of morphine-dependent mice that were treated with morphine-admixed food, while the withdrawal signs were completely suppressed in mice administered only 5 mg/kg morphine. These results suggest that the physical dependence liability of morphine type drugs can be predicted by the drug-admixed food method.