Howes J F
Pharmacol Biochem Behav. 1981 May;14(5):689-92. doi: 10.1016/0091-3057(81)90132-5.
The rat intraperitoneal infusion procedure was used to chronically administer drugs for evaluation of the physical dependence liability of narcotic antagonist analgesics. Three methods were used to assess dependence liability: presence of withdrawal signs upon abrupt cessation of chronic infusion (primary dependence), attenuation of the withdrawal signs produced by cessation of chronic morphine infusion (morphine substitution), and production of withdrawal signs when chronically morphine-fused rats were administered the drugs (precipitated withdrawal). Butorphanol, nalbuphine and pentazocine all caused a mild withdrawal in the rat primary dependence model which agrees with the conclusions from experiments with monkey and man. None of these agents substituted for morphine in the rat and three appeared to precipitate withdrawal. Two experimental drugs, Codorphone and TR5400, did not induce primary dependence in the rat, and in chroni-morphinized rats, they precipitated a withdrawal syndrome comparable to naloxone. Another experimental drug, TR5257, substituted for morphine. The correlation between these observations in the rat and previously published data from the monkey are excellent. It is proposed that the rat could be used as a reliable indicator of potential physical dependence liability for the narcotic antagonist analgesics.
采用大鼠腹腔内输注法长期给药，以评估麻醉性拮抗镇痛药产生身体依赖性的可能性。使用了三种方法来评估产生依赖性的可能性：长期输注突然停止时出现戒断症状（原发性依赖性）、停止长期吗啡输注所产生的戒断症状的减弱（吗啡替代），以及对长期接受吗啡输注的大鼠给药时产生戒断症状（诱发戒断）。布托啡诺、纳布啡和喷他佐辛在大鼠原发性依赖性模型中均引起轻度戒断，这与在猴和人身上进行的实验得出的结论一致。这些药物在大鼠中均不能替代吗啡，且三种药物似乎均可诱发戒断。两种实验药物，可多芬和TR5400，在大鼠中未诱发原发性依赖性，而在长期吗啡化的大鼠中，它们诱发了与纳洛酮相当的戒断综合征。另一种实验药物TR5257可替代吗啡。大鼠中的这些观察结果与先前发表的来自猴的数据之间的相关性极佳。有人提出，大鼠可作为麻醉性拮抗镇痛药潜在身体依赖性可能性的可靠指标。
