Gellert V F, Sparber S B
J Pharmacol Exp Ther. 1977 Apr;201(1):44-54.
Rats were trained to press a lever (respond) under a fixed-ratio 20 schedule for food presentation. Administration of 10 or 25 mg of naloxone (NX) per kg i.p. to drug-naive rats supressed responding whereas 1 mg of NX per kg was without effect. However, administration of 0.25 mg of NX per kg to rats which had received 10 or 15 mg of morphine sulfate per kg 48 hours previously induced small, but statistically reliable, decrements in responding. Rats implanted with one pellet containing 75 mg of morphine base displayed tolerance to the depressant effects of the morphine pellet within 2 days after implantation. A systematic study of the effects of naloxone given to morphine tolerant-dependent rats revealed good concordance between the amount of weight lost and the severity of behavioral disruption, within the same subject, after administration of the antagonist. Although 0.03 mg of NX per kg given 3 to 6 days after pellet implantation significantly suppressed responding, 0.1 mg of NX per kg was required to produce a significant reduction in body weight. Semiweekly injections of 1 mg of NX per kg continued to suppress responding up to 4 weeks after implantation of a single morphine pellet. The body weight changes were significant only up to 3 weeks after implantation. The data suggest that disruption of fixed-ratio responding is a sensitive indicator of antagonist-precipitated morphine withdrawal.
训练大鼠在固定比率为20的实验安排下按压杠杆（做出反应）以获取食物。对未接触过药物的大鼠腹腔注射每千克10或25毫克的纳洛酮（NX）会抑制反应，而每千克1毫克的NX则无此效果。然而，对48小时前已接受每千克10或15毫克硫酸吗啡的大鼠腹腔注射每千克0.25毫克的NX，会导致反应出现微小但在统计学上可靠的下降。植入一枚含有75毫克吗啡碱的丸剂的大鼠在植入后2天内对吗啡丸剂的抑制作用产生了耐受性。一项对给予吗啡耐受依赖大鼠纳洛酮效果的系统研究表明，在同一实验对象中，给予拮抗剂后体重减轻的量与行为扰乱的严重程度之间具有良好的一致性。尽管在丸剂植入后3至6天给予每千克0.03毫克的NX可显著抑制反应，但每千克0.1毫克的NX才能使体重显著下降。在植入单一吗啡丸剂后，每周两次注射每千克1毫克的NX在长达4周的时间内持续抑制反应。体重变化仅在植入后3周内显著。数据表明，固定比率反应的扰乱是拮抗剂诱发吗啡戒断的敏感指标。
