Marek P, Mogil J S, Sternberg W F, Panocka I, Liebeskind J C
Department of Psychology, University of California, Los Angeles 90024-1563.
Brain Res. 1992 Apr 24;578(1-2):197-203. doi: 10.1016/0006-8993(92)90248-8.
The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (dizocilpine, 0.075 mg/kg, i.p.) on swim-stress-induced analgesia (SSIA) were studied in control (C) mice and in mice selectively bred for high (HA) or low (LA) SSIA. In three consecutive experiments, animals were subjected to forced swimming at water temperature of 20 degrees C, 32 degrees C and 15 degrees C and the resulting analgesia (hot-plate test) was found to be mixed opioid/non-opioid, opioid and non-opioid, respectively, as a function of the degree of antagonism by naloxone (10 mg/kg, i.p.). The major finding of this study is that MK-801 attenuated 15 degrees C SSIA, against which naloxone was ineffective, but had no effect on 32 degrees C SSIA, which naloxone blocked completely. A combination of naloxone and MK-801 significantly attenuated 20 degrees C SSIA in C and HA mice and in HA mice this attenuation was significantly larger than that produced by either drug alone. Morphine analgesia (10 mg/kg, i.p.) was unaffected by MK-801. It is concluded that low doses of MK-801 selectively block non-opioid mechanisms of SSIA.
在对照（C）小鼠以及选择性培育出的高应激游泳诱导镇痛（SSIA）（HA）或低应激游泳诱导镇痛（LA）小鼠中，研究了特异性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801（地佐环平，0.075毫克/千克，腹腔注射）对游泳应激诱导镇痛（SSIA）的影响。在连续三个实验中，动物分别在20摄氏度、32摄氏度和15摄氏度的水温下进行强迫游泳，结果发现产生的镇痛作用（热板试验）分别是混合性阿片类/非阿片类、阿片类和非阿片类，这取决于纳洛酮（10毫克/千克，腹腔注射）的拮抗程度。本研究的主要发现是，MK-801减弱了15摄氏度时的SSIA，对此纳洛酮无效，但对32摄氏度时的SSIA没有影响，而纳洛酮可完全阻断该温度下的SSIA。纳洛酮和MK-801联合使用可显著减弱C组和HA组小鼠20摄氏度时的SSIA，并且在HA组小鼠中，这种减弱作用明显大于单独使用任何一种药物时产生的效果。吗啡镇痛作用（10毫克/千克，腹腔注射）不受MK-801影响。得出的结论是，低剂量的MK-801选择性阻断SSIA的非阿片类机制。
