Wahba Z Z, Oriaku E T, Soliman K F
Pharmacology. 1987;34(2-3):66-73. doi: 10.1159/000138254.
In this study, male Sprague-Dawley rats maintained under controlled environmental conditions were used. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in cerebral cortex, bulbus olfactorius, midbrain, hypothalamus, hippocampus, cerebellum, pons and medulla oblongata in control rats and rats treated with morphine (10 mg/kg) for 1 or 2 days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced. Significant increase (p less than 0.01) in AChE activity of the medulla oblongata was observed following morphine administration for 1 or 2 days. A single injection of morphine resulted in a significant decline (p less than 0.01) in ChAT activity of hypothalamus, cerebellum and medulla oblongata. However, no such decline could be observed after 2 consecutive daily injections of morphine. In the cerebral cortex there was a significant decline (p less than 0.01) in ChAT activity after the second administration of morphine. These findings indicate that the changes in the responsiveness of the brain cholinergic enzymes following repeated morphine administration may in part explain the rapid development of tolerance to the analgesic effect of morphine.
在本研究中，使用了在可控环境条件下饲养的雄性Sprague-Dawley大鼠。测定了对照大鼠和用吗啡（10mg/kg）处理1天或2天的大鼠大脑皮质、嗅球、中脑、下丘脑、海马体、小脑、脑桥和延髓中的胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）活性。重复给予吗啡与所产生的镇痛程度下降有关。在给予吗啡1天或2天后，观察到延髓的AChE活性显著增加（p<0.01）。单次注射吗啡导致下丘脑、小脑和延髓的ChAT活性显著下降（p<0.01）。然而，连续每日注射吗啡2次后未观察到这种下降。在大脑皮质中，第二次给予吗啡后ChAT活性显著下降（p<0.01）。这些发现表明，重复给予吗啡后大脑胆碱能酶反应性的变化可能部分解释了对吗啡镇痛作用快速产生耐受性的原因。
