PROLONGED TOLERANCE, DEPENDENCE AND ABSTINENCE FOLLOWING SUBCUTANEOUS MORPHINE PELLET IMPLANTATION IN THE RAT
PROLONGED TOLERANCE, DEPENDENCE AND ABSTINENCE FOLLOWING SUBCUTANEOUS MORPHINE PELLET IMPLANTATION IN THE RAT
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DOI：
10.1016/0014-2999(94)90755-2
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发表时间：
1994-02-21
影响因子：
5
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
GOLD, LH;STINUS, L;KOOB, GF
阿片戒断是人类阿片成瘾者中常见的现象，不会危及生命，但被认为是可能导致这些阿片依赖者吸毒行为的一个重要因素。本研究的目的是使用大鼠模型来比较耐受、依赖和戒断发展的时间过程。通过皮下植入 2 粒吗啡颗粒使大鼠产生依赖。 （75 毫克吗啡碱）。植入吗啡的大鼠在植入后长达 12 小时内表现出镇痛作用（通过尾浸试验测得），此后耐受性的发展导致甩尾潜伏期恢复到对照大鼠的水平。通过注射阿片拮抗剂纳洛酮（1 mg/kg s.c.）来评估戒断情况。戒断综合征的评级显示植入后 3 小时有明显的戒断症状，并且在植入后 24 小时内变得越来越强烈。植入后至少 13 天可能会出现戒断症状，而到植入后 18 天几乎没有观察到戒断迹象。植入 2 个颗粒后，血浆吗啡水平在植入后 3-12 天保持相对稳定。这些结果进一步扩展了皮下颗粒植入后阿片戒断的特征。这些结果还表明，阿片类药物戒断是在最初 24 小时内形成的，并且遵循耐受性发展的时间进程。在类似的实验条件下描述阿片类药物耐受性、身体依赖性和戒断的演变对于设计未来研究这些现象的神经基础至关重要。
Opiate withdrawal is a common occurrence in human opiate addicts that is not life threatening but is hypothesized to be a significant factor which may contribute to drug taking behavior in these opiate dependent individuals. The purpose of this study was to compare the time course for the development of tolerance, dependence and abstinence using a rat model. Rats were made dependent by implantation of 2 morphine pellets s.c. (75 mg morphine base). Morphine implanted rats exhibited analgesia as measured in a tail-dip assay, for up to 12 h post-implant after which the development of tolerance resulted in tail-flick latencies returning to the level of control rats. Withdrawal was evaluated by injection of the opiate antagonist, naloxone (1 mg/kg s.c.). Rating of the abstinence syndrome revealed significant withdrawal signs by 3 h post-implant which became increasingly intense up to 24 h post-implant. Withdrawal could be precipitated for at least 13 days post-implant, while by 18 days post-implant almost no abstinence signs were observed. Plasma morphine levels following implantation of 2 pellets remained relatively stable from 3-12 days post-implantation. These results further extend the characterization of opiate abstinence following subcutaneous pellet implantation. These results also suggest that opiate abstinence develops within the first 24 h and follows the time course of the development of tolerance. The characterization of the evolution of opiate tolerance, physical dependence and abstinence under similar experimental conditions is critical to the design of future studies to examine the neural bases for these phenomena.