NMDA RECEPTOR ANTAGONISTS AND OPIOID TOLERANCE

对啮齿动物的研究表明，化学物质可以发挥作用 NU-甲基-D-天冬氨酸(NMDA)谷氨酸受体抑制发育 对吗啡的抗伤害作用的耐受性以及 逆转预先存在的吗啡。为了支持这种交互 作为阿片类药物耐受的普遍现象，并支持其 可能在人体上应用，建议的一系列实验是 旨在将这些发现扩展到)临床上有用的穆阿片类药物 除了吗啡和b)抗伤害感受的灵长类模型。因此， 实验一和实验二采用大鼠撤尾实验来检验 竞争性NMDA受体拮抗剂对发育的影响 吗啡和其他阿片类药物的抗伤害性作用 它们在阿片受体上的内在效力各不相同。 实验三检验非竞争性NMDA受体的作用 Anagoist，一种竞争性的NMDA受体拮抗剂，以及甘氨酸部分 激动剂对吗啡耐受松鼠的抗痛作用 猴子在电击滴定试验中做出反应。

Research in rodents demonstraties that chemicals that functioning of the Nu-methyl-D-asparte(NMDA) glutamate receptor attenuate the development of tolerance to the antinociceptive effects of morphine as well as reverse pre-existing to morphine. In order to support this interaction as a general phenomenon of opioid tolerance and lend support to its possible application in humans, the proposed series of experiments is designed to extend these findings to a ) clinically-useful mu-opiods other than morphine and b) a primate model of antinoception. Thus, Experiments I and II employ a rat tail-withdrawal proecdure to examine the effects of a competivie NMDA receptor anatagonist on the development of toloerance to be antinoceptive effects of morphine and other opioid that vary on their intrinsic efficacy at the mu-opioid receptor. Experiment III examines the effects of non-competive NMDA receptor antagoist, a competitive NMDA receptor antagnist, and a glycine partial agonist on the antinocieptive effects of morphine-tolerant squirrel monkeys responding under a shock titration proedure.