The concentration of morphine in serum of rats made dependent using a drug-admixed food method.

The present study reports on the induction of physical dependence in rats using morphine-admixed food and addresses the question of the resulting concentration of morphine in serum. The stability of morphine in food is good, since no decrease in concentration could be observed. The concentration of morphine in serum during the experiment was measured using a radioimmunoassay technique. A correlation was found between the food intake during a 7-hour period and the concentration of morphine in the serum at the end of that period, both for a 1 g/kg and a 2 g/kg batch of morphine-admixed food. The concentration of morphine in serum was also found to be dose-related during a period of 6-23 days when the rats were fed for a prolonged period. After long-term administration of 1 g/kg morphine in food a steady-state level of about 0.5 mg/l serum was obtained. Similarly with 2 g/kg morphine in food a steady-state level of 0.8-1.1 mg/l serum was reached. After withdrawal of morphine the serum concentration of morphine dropped to 0.1 mg/l within 24 hours and to below the detection limit within 48 hours. During the withdrawal period sharp drops were noted in body weight (20%) and food intake (50%) after one day.