INHIBITION OF MORPHINE-TOLERANCE AND DEPENDENCE BY THE NMDA RECEPTOR ANTAGONIST MK-801
INHIBITION OF MORPHINE-TOLERANCE AND DEPENDENCE BY THE NMDA RECEPTOR ANTAGONIST MK-801
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DOI：
10.1126/science.1824728
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发表时间：
1991-01-04
期刊：
影响因子：
56.9
通讯作者：
AKIL, H
中科院分区：
文献类型：
--
作者：
TRUJILLO, KA;AKIL, H
谷氨酸受体的N-甲基-D-天冬氨酸(NMDA)亚型是多种神经和行为可塑性的重要介体。目前的研究考察了NMDA受体是否可能参与阿片类药物耐受和依赖的发展，这是行为可塑性的两个例子。非竞争性NMDA受体拮抗剂MK-801在不影响急性吗啡镇痛作用的情况下，可减轻对吗啡镇痛作用的耐受性。此外，根据纳洛酮催促戒断的评估，MK-801可减轻吗啡依赖的发展。这些结果表明，NMDA受体可能在阿片类药物耐受和依赖的形成中起重要作用。
The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by nalox-one-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.