Suzuki T, Yoshii T, Yanaura S
Jpn J Pharmacol. 1984 Mar;34(3):319-25. doi: 10.1254/jjp.34.319.
The drug-admixed food method was applied to ICR strain mice for studying development of physical dependence on morphine. Mice were treated with morphine-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. During the treatment, the mice did not show any signs of toxicity. Plasma and brain morphine levels were quantitatively related to the morphine concentration in drug-admixed food. The plasma morphine level showed a circadian rhythm, and the level was higher than 0.15 microgram/ml throughout the day. The morphine-treated mice manifested body weight loss, diarrhea and ptosis from 4 hr after morphine withdrawal and showed maximum body weight loss at 12 hr. In the naloxone-precipitated test, jumping and body shakes were observed in mice treated with morphine-admixed food (2 mg/g food) at least for 1 day. Moreover, in mice treated with morphine (2 mg/g food) for 3 days, marked jumping and body shakes and some writhing were observed after naloxone administration. These results suggest that the drug-admixed food method has advantages of easily and rapidly inducing the physical dependence on morphine in mice without causing toxicity and death.
采用药物掺食法对ICR品系小鼠进行研究，以探讨吗啡身体依赖性的形成。每隔一天用浓度递增（1、2和3mg/g食物）的吗啡掺食小鼠，持续9天。治疗期间，小鼠未出现任何毒性迹象。血浆和脑内吗啡水平与掺食药物中吗啡浓度呈定量关系。血浆吗啡水平呈现昼夜节律，且全天均高于0.15微克/毫升。吗啡处理的小鼠在撤药后4小时开始出现体重减轻、腹泻和眼睑下垂，并在12小时时体重减轻达到最大值。在纳洛酮激发试验中，至少用含2mg/g食物的吗啡掺食处理1天的小鼠出现跳跃和身体颤抖。此外，用含2mg/g食物的吗啡处理3天的小鼠，在给予纳洛酮后出现明显的跳跃、身体颤抖和一些扭体反应。这些结果表明，药物掺食法具有在不引起毒性和死亡的情况下，轻松快速诱导小鼠对吗啡产生身体依赖性的优点。
