A new ingestion method for long-term morphine intoxication in rat.

A new method for long-term morphine intoxication in rat was developed. It was designed to deal with the nutritional imbalance and body weight loss that generally occurs using conventional techniques for morphine treatment. The morphine is administered in a nutritionally complete diet. Also pair-feeding is used to deal with intoxicated rats that do not eat the same amount of food as controls. The technique was validated during the study of different intoxication conditions, using different initial doses, dose increments and final doses. An initial dose of 25 mg morphine/kg b.w., raised exponentially up to 340 mg/kg b.w. in 8 days, made the rats dependent, as tested by withdrawal signs, precipitated by excluding morphine from the diet, or by administration of antagonists. A final dose of up to 715 mg morphine/kg b.w. was reached in 13 days without decreased food intake. However, initial doses of 340 or 715 mg/kg led to impaired weight gain and diet consumption. Plasma morphine levels of 3 micrograms/ml serum were reached on a dose of 340 mg/kg b.w. Also, preference for morphine diet over control diet was evaluated by choice tests. The technique is simple, time-saving and inexpensive, allowing the treatment of numerous animals for long periods under standardized intoxication conditions. No animals get ill or die.