van der Laan J W, Loeber J G, de Groot G, Sekhuis V M
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Pharmacol Biochem Behav. 1988 Sep;31(1):123-8. doi: 10.1016/0091-3057(88)90322-x.
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.
本研究报告了使用含吗啡食物诱导大鼠产生身体依赖性的情况，并探讨了血清中吗啡的最终浓度问题。吗啡在食物中的稳定性良好，因为未观察到浓度下降。实验期间血清中的吗啡浓度采用放射免疫测定技术进行测量。对于1 g/kg和2 g/kg批次的含吗啡食物，在7小时内的食物摄入量与该时间段结束时血清中的吗啡浓度之间均发现存在相关性。在大鼠长期喂食6 - 23天期间，血清中的吗啡浓度也与剂量相关。长期给大鼠喂食含1 g/kg吗啡的食物后，血清中达到了约0.5 mg/l的稳态水平。同样，喂食含2 g/kg吗啡的食物后，血清中达到了0.8 - 1.1 mg/l的稳态水平。停用吗啡后，血清中的吗啡浓度在24小时内降至0.1 mg/l，并在48小时内降至检测限以下。在戒断期，一天后体重（下降20%）和食物摄入量（下降50%）出现急剧下降。
