Eisenberg R M
Life Sci. 1982 Apr 19;30(16):1399-405. doi: 10.1016/0024-3205(82)90026-1.
Short-term tolerance to opiates has been demonstrated in as little as three hours after priming with a single dose of morphine in naive animals. Tail-flick latency in mice and changes in plasma corticosterone in rats were the indicators tested in these experiments. Rats primed wiht either saline or morphine, 10 mg/kg, were injected 3 hrs. subsequently with morphine, 5 mg/kg. Those primed with saline showed the characteristic plasma corticosterone elevation following morphine, when serial blood samples were examined, whereas those previously treated with morphine did not. Mice were primed with saline or either of two doses of morphine, 30 or 100 mg/kg, 3.5 hrs. prior to estimation of tail-flick latency and ED50 determinations. Mice primed with either dose of morphine had significantly higher ED50's than those primed with saline. The effects of indomethacin, 5 or 10 mg/kg, were examined on both systems. Rats and mice were pretreated with indomethacin at 2.25 or 3 hrs., respectively, before morphine-priming. In all cases, indomethacin did not produce alterations in responses previously observed in correspondently treated controls.
在未接触过药物的动物中，单次注射吗啡引发作用后短短三小时就已证实存在对阿片类药物的短期耐受性。这些实验中所检测的指标是小鼠的甩尾潜伏期以及大鼠血浆皮质酮的变化。用生理盐水或10mg/kg吗啡进行引发处理的大鼠，3小时后再注射5mg/kg吗啡。当对系列血样进行检测时，用生理盐水引发处理的大鼠在注射吗啡后出现了典型的血浆皮质酮升高，而先前用吗啡处理过的大鼠则未出现这种情况。在评估甩尾潜伏期和半数有效剂量（ED50）测定前3.5小时，用生理盐水或两种剂量（30mg/kg或100mg/kg）的吗啡之一对小鼠进行引发处理。用任一剂量吗啡引发处理的小鼠其半数有效剂量均显著高于用生理盐水引发处理的小鼠。研究了5mg/kg或10mg/kg吲哚美辛对这两个系统的影响。在对大鼠和小鼠用吗啡进行引发处理前，分别提前2.25小时或3小时用吲哚美辛进行预处理。在所有情况下，吲哚美辛均未对相应处理的对照组中先前观察到的反应产生改变。
