en Pharmacology Pharmacology Original Research: Basic Science in Medicine Original Research: Basic Science in Medicine The effect of NMDA (N-methyl-D-aspartate) receptor antagonists on tolerance to morphine antinociception was investigated in mice. Daily subcutaneous administration of 50 mg/kg of morphine hydrochloride for three days induced tolerance to different (3,6 and 9 mg/kg) test doses of morphine. The tolerance obtained was decreased by pretreatment of animals with single or repeated doses of competitive NMDA receptor antagonists D-( -)-2-amino-5-phosphonovaleric acid (DAP5 0.1-0.3 mg/kg) and D-(-)-2-amino-7-phosphonoheptanoic acid (DAP7 0.1-0.3 mg/kg). Tolerance to morphine response was also obtained 7, 14, 21 and 30 days after unilateral sciatic nerve ligation. Single or repeated doses (0.2 mg/kg) of DAP5 or DAP7 increased the antinociceptive response induced by morphine (9 mg/kg) in the nerve ligated animals. We report that these agents attenuate the development of morphine tolerance, and increase the antinociceptive effect of morphine on sciatic neuropathic pain in mice. 41 47 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-298-278&slc_lang=en&sid=1 GR TAGHIZADEH-JAHROMI 20031947532846004240 20031947532846004240 No M REZAYAT 20031947532846004241 20031947532846004241 No MR ZARRINDAST 20031947532846004242 20031947532846004242 Yes From the Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran.