NMDA RECEPTOR ANTAGONISTS AND OPIOID TOLERANCE

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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.