Development of physical dependence on and tolerance to morphine in rats treated with morphine-admixed food.

1. The development process of physical dependence on and tolerance to morphine has been explored in rats treated with morphine-admixed food (0.5 mg/g of food) during 1 to 7 days. 2. In the morphine-treated animals, body weight loss was observed after the abrupt morphine withdrawal. 3. Intensity and time course of the weight loss were correlated to the morphine treatment. 4. On the other hand, the morphine-treated rats showed abnormal behaviors, such as diarrhea, ptosis, teeth chattering, salivation, body shakes, vocalization, nose bleed, irritability, aggression, lacrimation and writhing upon naloxone injection. 5. Loss of body weight, measured 3 hours after naloxone injection, was also correlated to the duration of morphine treatment. 6. Tolerance to the analgesic effect of morphine developed within one day in rats treated with morphine-admixed food. 7. The drug-admixed food ingestion method has the advantage of rapidly inducing a high degree of physical dependence and tolerance without causing morbidity or lethality in animals. It also eliminates the need for excessive handling of animals.