Suzuki T, Shimada M, Yoshii T, Yanaura S
Jpn J Pharmacol. 1984 Apr;34(4):441-6. doi: 10.1254/jjp.34.441.
The developmental process of physical dependence on codeine has been explored in rats treated with codeine-admixed food (0.5 mg/g food) during 1 to 7 days. In rats treated with codeine for more than 2 days, body weight loss was markedly observed after the abrupt codeine withdrawal. The intensity and time course of body weight loss increased according to the duration of codeine treatment. After the codeine withdrawal, behavioral signs such as diarrhea, ptosis and vocalization were observed. In the naloxone-precipitated withdrawal test, rats treated with codeine for 1 day manifested a loss of body weight after naloxone challenge, and the intensity of body weight loss increased according to the duration of codeine treatment. After naloxone injection, the codeine-treated rats showed abnormal behaviors such as diarrhea, ptosis, teeth chattering , salivation, body shakes, vocalization, nose bleed, irritability, lacrimation and writhing. The total score, evaluated by the ranking system for precipitated withdrawal behaviors, was correlated with the duration of codeine treatment. These results suggest that naloxone-precipitated withdrawal signs are powerful in comparison with that after codeine withdrawal, and the weight loss is a common index for quantitative assessment of physical dependence on narcotics in the natural and naloxone-precipitated withdrawal tests. It is concluded that the drug-admixed food ingestion method has the advantage of rapidly inducing a high degree of physical dependence on codeine.
在1至7天内，用含可待因食物（0.5毫克/克食物）喂养大鼠，对大鼠身体依赖可待因的发育过程进行了研究。在用可待因治疗超过2天的大鼠中，突然停用可待因后明显观察到体重减轻。体重减轻的强度和时间进程根据可待因治疗的持续时间而增加。停用可待因后，观察到腹泻、眼睑下垂和鸣叫等行为体征。在纳洛酮诱发的戒断试验中，用可待因治疗1天的大鼠在纳洛酮激发后出现体重减轻，体重减轻的强度根据可待因治疗的持续时间而增加。注射纳洛酮后，用可待因治疗的大鼠表现出腹泻、眼睑下垂、牙齿打颤、流涎、身体颤抖、鸣叫、鼻出血、易怒、流泪和扭体等异常行为。通过诱发戒断行为分级系统评估的总分与可待因治疗的持续时间相关。这些结果表明，与可待因戒断后的情况相比，纳洛酮诱发的戒断体征更为明显，并且体重减轻是在自然戒断和纳洛酮诱发的戒断试验中对麻醉药品身体依赖进行定量评估的常用指标。得出的结论是，药物混合食物摄入法具有快速诱导对可待因高度身体依赖的优点。
