Validation of spontaneous morphine withdrawal symptoms in rats

Spontaneous morphine withdrawal has been studied in rats after induction of dependence using administration of morphine via the food (+/- 160 mg/kg/day on the basis of body weight). In the present paper, the decrease of the nocturnal locomotor activity and of food intake were validated as real morphine withdrawal symptoms. During the withdrawal phase, morphine was readministered either by subcutaneous injection of morphine or admixed in the food. Subcutaneous administration resulted in short-lasting enhancements (of 50%) of the locomotor activity (peak effects) followed by a decrease of 50%, while food intake and loss of body weight were hardly affected. Administration via the food resulted in a dose-dependent reduction of the decrease of the nocturnal locomotor activity, the decrease in food intake and the loss of body weight. Chronic naloxone infusion (0.03 or 0.1 mg/kg/hr) via osmotic minipumps appeared to have similar effects on locomotor activity, food intake and body weight, compared with spontaneous withdrawal of morphine. However, the recovery to normal values appeared to occur faster after naloxone infusion. It is concluded that the observed withdrawal symptoms, i.e. decrease of the locomotor activity, decrease of food intake and loss of body weight, can be interpreted as real withdrawal symptoms not caused by additional manipulations occurring in the course of the experiments.