Suzuki T, Fukagawa Y, Yoshii T, Yanaura S, Katz J L
Department of Pharmacology, Hoshi University, Tokyo, Japan.
Life Sci. 1989;45(14):1237-46. doi: 10.1016/0024-3205(89)90125-2.
Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.
通过将吗啡与小鼠食物混合（2毫克/克）三天，使小鼠对吗啡产生依赖性。递增剂量的纳洛酮引发了剂量依赖性的戒断反应，如体重减轻和跳跃。这些戒断反应可被吗啡预处理所拮抗。在非依赖性和依赖性个体中，纳洛酮均可拮抗吗啡的作用，如增加运动活性、抑制肠道转运和镇痛。在依赖性个体中，纳洛酮的拮抗作用增强；较低剂量的纳洛酮就足以拮抗吗啡的作用。目前的结果证实了早期的研究，表明吗啡预处理可拮抗戒断反应的诱发，提示戒断反应是由于纳洛酮作用于阿片类激动剂所作用的同一受体。纳洛酮在依赖性个体中拮抗效力的增加，将早期关于镇痛作用的结果扩展到吗啡的其他几种激动剂作用，并且与以下解释一致，即暴露于阿片类激动剂会诱导阿片受体构象的改变。
