Bhargava H N, Zhao G M
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612, USA.
Brain Res. 1996 May 6;719(1-2):56-61. doi: 10.1016/0006-8993(96)00112-6.
The effects of MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and of LY 235959, a competitive antagonist of the NMDA receptor on the analgesic action and development of tolerance to the analgesic action of D-Ala2, Glu4 deltorphin II (deltorphin II), a delta 2-opioid receptor agonist were determined in mice. Tolerance to deltorphin II was induced in male Swiss-Webster mice by twice daily intracerebroventricular (i.c.v.) injections of the drug (20 micrograms/mouse) for 4 days. To determine the effects of NMDA receptor antagonists, the drugs were injected intraperitoneally in appropriate doses 10 min before each injection of deltorphin II. The doses of MK-801 were 0.01, 0.03 or 0.10 mg/kg whereas those of LY 235959 were 1, 2 or 4 mg/kg. Chronic administration of NMDA receptor antagonists by themselves did not alter the tail-flick latency or the analgesic effect of deltorphin II. MK-801 given concurrently with deltorphin II inhibited the development of tolerance to deltorphin II, the significant effects were observed at 0.03 and 0.10 mg/kg doses. Similar inhibitory effect of development of tolerance to deltorphin II were observed with LY 235959 at 4 mg/kg dose. MK-801 and LY 235959 also antagonized the analgesic action of deltorphin II. It is concluded that antagonism of NMDA receptors attenuates the analgesic action as well as development of tolerance to the analgesic action of delta 2-opioid receptor agonist in the mouse.
在小鼠中测定了N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂MK-801以及NMDA受体的竞争性拮抗剂LY 235959对D-Ala2、Glu4 强啡肽II（强啡肽II）（一种δ2阿片受体激动剂）镇痛作用及镇痛耐受性形成的影响。雄性瑞士-韦伯斯特小鼠通过每天两次脑室内（i.c.v.）注射该药物（20微克/小鼠），持续4天来诱导对强啡肽II的耐受性。为了测定NMDA受体拮抗剂的作用，在每次注射强啡肽II前10分钟腹腔注射适当剂量的药物。MK-801的剂量为0.01、0.03或0.10毫克/千克，而LY 235959的剂量为1、2或4毫克/千克。单独长期给予NMDA受体拮抗剂不会改变甩尾潜伏期或强啡肽II的镇痛效果。与强啡肽II同时给予MK-801可抑制对强啡肽II耐受性的形成，在0.03和0.10毫克/千克剂量时观察到显著效果。在4毫克/千克剂量的LY 235959下也观察到对强啡肽II耐受性形成的类似抑制作用。MK-801和LY 235959也拮抗强啡肽II的镇痛作用。得出的结论是，NMDA受体的拮抗作用减弱了小鼠中δ2阿片受体激动剂的镇痛作用以及镇痛耐受性的形成。
