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.
| Allen, R M; Dykstra, L A (2001) N-methyl-D-aspartate receptor antagonists potentiate the antinociceptive effects of morphine in squirrel monkeys. J Pharmacol Exp Ther 298:288-97 |
| Allen, R M; Dykstra, L A (2000) Attenuation of mu-opioid tolerance and cross-tolerance by the competitive N-methyl-D-aspartate receptor antagonist LY235959 is related to tolerance and cross-tolerance magnitude. J Pharmacol Exp Ther 295:1012-21 |
| Allen, R M; Dykstra, L A (2000) Role of morphine maintenance dose in the development of tolerance and its attenuation by an NMDA receptor antagonist. Psychopharmacology (Berl) 148:59-65 |
