Tseng L F, Lin J J, Collins K A
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Eur J Pharmacol. 1993 Sep 7;241(1):63-70. doi: 10.1016/0014-2999(93)90933-9.
The effects of subcutaneous morphine pellet-implantation on antinociception induced by intracerebroventricular (i.c.v.) administration of beta-endorphin or morphine and intrathecal (i.t.) administration of morphine, [D-Pen2,D-Pen5]enkephalin (DPDPE), [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), serotonin or norepinephrine were studied in male ICR mice. The tail-flick and hot-plate responses were used for antinociceptive tests. The ED50 values for i.c.v. administered morphine for antinociception in morphine pellet-implanted mice were increased from 3.3- and 2.2-fold at 0 h to 14.2- and 19.0-fold at 4 h and declined to 4.8- and 3.0-fold at 8 h after pellet removal in the tail-flick and hot-plate tests, respectively. On the other hand, the ED50 values for i.c.v. administered beta-endorphin for antinociception were only slightly increased (1.7- to 5.1-fold increases) throughout the same time course. The inhibition of the tail-flick response induced by i.t. injection of morphine, DPDPE and serotonin, but not norepinephrine or DAMGO, was attenuated in morphine pellet-implanted mice. These findings are consistent with previous studies indicating that different neuronal mechanisms are involved in morphine- and beta-endorphin-induced antinociception.
在雄性ICR小鼠中研究了皮下植入吗啡微丸对脑室内（i.c.v.）注射β-内啡肽或吗啡以及鞘内（i.t.）注射吗啡、[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE）、[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇]脑啡肽（DAMGO）、5-羟色胺或去甲肾上腺素所诱导的镇痛作用的影响。采用甩尾和热板反应进行镇痛测试。在甩尾和热板试验中，植入吗啡微丸的小鼠，i.c.v.注射吗啡产生镇痛作用的半数有效剂量（ED50）值在移除微丸后0小时分别从3.3倍和2.2倍增加到4小时的14.2倍和19.0倍，并在8小时分别降至4.8倍和3.0倍。另一方面，在整个相同时间段内，i.c.v.注射β-内啡肽产生镇痛作用的ED50值仅略有增加（增加1.7至5.1倍）。在植入吗啡微丸的小鼠中，i.t.注射吗啡、DPDPE和5-羟色胺诱导的甩尾反应抑制作用减弱，但去甲肾上腺素或DAMGO诱导的甩尾反应抑制作用未减弱。这些发现与先前的研究一致，表明吗啡和β-内啡肽诱导的镇痛作用涉及不同的神经元机制。
