Sasson S, Unterwald E M, Kornetsky C
Psychopharmacology (Berl). 1986;90(2):163-5. doi: 10.1007/BF00181233.
Rats were trained to escape from aversive electrical brain stimulation delivered to the mesencephalic reticular formation (MRF). The threshold for this escape behavior was determined by a modification of the classic psychophysical method of limits. Escape thresholds were determined after the administration of morphine alone, d-amphetamine alone, and the combination of d-amphetamine and an ineffective dose of morphine. Morphine alone caused a dose-dependent raising of the escape threshold (1.0-16.0 mg/kg IP) while d-amphetamine alone (0.06-2.0 mg/kg IP) had no effect or caused a slight lowering of threshold. For each animal, a dose of morphine that produced no change in escape threshold was then selected to be administered concomitantly with various doses of d-amphetamine. The co-administration of morphine and d-amphetamine resulted in a significant, dose-dependent increase in the escape threshold, which was not seen with d-amphetamine alone and was as great or greater in magnitude than the increase seen with the highest dose of morphine tested. The results of this study clearly demonstrate that opiate analgesia is potentiated by concomitant d-amphetamine administration. The mechanisms involved in this potentiation warrant further investigation for the clinical management of pain.
训练大鼠逃避施加于中脑网状结构（MRF）的厌恶性脑电刺激。这种逃避行为的阈值通过对经典的极限法心理物理学方法进行修改来确定。在单独给予吗啡、单独给予右旋苯丙胺以及给予右旋苯丙胺与无效剂量吗啡的组合后，测定逃避阈值。单独给予吗啡会导致逃避阈值呈剂量依赖性升高（腹腔注射1.0 - 16.0毫克/千克），而单独给予右旋苯丙胺（腹腔注射0.06 - 2.0毫克/千克）则没有效果或导致阈值略有降低。然后为每只动物选择一个对逃避阈值没有影响的吗啡剂量，与各种剂量的右旋苯丙胺同时给药。吗啡和右旋苯丙胺联合给药导致逃避阈值显著且呈剂量依赖性增加，这在单独使用右旋苯丙胺时未观察到，并且在幅度上与测试的最高剂量吗啡所导致的增加相同或更大。这项研究的结果清楚地表明，同时给予右旋苯丙胺可增强阿片类镇痛作用。这种增强作用所涉及的机制值得进一步研究以用于疼痛的临床管理。
