Hoffmann O, Wiesenfeld-Hallin Z
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Neuroreport. 1996 Feb 29;7(3):838-40. doi: 10.1097/00001756-199602290-00037.
The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a role in the development and reversal of tolerance to morphine. In morphine-tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine on the hot plate test. However, combined administration of CI 988 and dextromethorphan did not further potentiate the antinociceptive effect of morphine in tolerant rats. Dextromethorphan by itself had no effect in tolerant rats. In drug-naive rats, dextromethorphan by itself had no antinociceptive effect, but when combined with morphine or morphine and CI 988, it significantly potentiated the magnitude and duration of the effect of morphine. Thus, unlike the reversal of tolerance with CI 988 at doses that did not potentiate the effect of morphine, the antinociception observed with the NMDA antagonist in the presence of morphine in tolerant rats may not represent the reversal of tolerance, but may instead reflect the potentiation of morphine's analgesic effect by dextromethorphan.
N-甲基-D-天冬氨酸（NMDA）受体和胆囊收缩素-B（CCK-B）受体可能在吗啡耐受性的产生及耐受性的逆转中发挥作用。在吗啡耐受的大鼠中，添加CCK-B受体拮抗剂CI 988或NMDA受体阻滞剂右美沙芬可增强吗啡在热板试验中的镇痛作用。然而，CI 988和右美沙芬联合给药并未进一步增强吗啡对耐受大鼠的镇痛作用。右美沙芬单独使用对耐受大鼠没有作用。在未接触过药物的大鼠中，右美沙芬单独使用没有镇痛作用，但与吗啡或吗啡及CI 988联合使用时，可显著增强吗啡作用的强度和持续时间。因此，与在不增强吗啡作用剂量下用CI 988逆转耐受性不同，在耐受大鼠中，NMDA拮抗剂与吗啡同时使用时观察到的镇痛作用可能并不代表耐受性的逆转，而可能反映了右美沙芬对吗啡镇痛作用的增强。
