Young G A, Khazan N
Eur J Pharmacol. 1986 Jun 17;125(2):265-71. doi: 10.1016/0014-2999(86)90036-1.
One group of six adult female Sprague-Dawley rats was given a series of automatically administered i.v. morphine injections over eight days. Similarly, a second group of six rats was given ethylketocyclazocine (EKC). Control rats received chronic i.v. saline injections. Tolerance to EEG and behavioral effects of morphine and EKC was demonstrated. At 15 days morphine post-withdrawal, morphine challenges produced EEG and behavioral stupor for a mean of 5 min, followed by EEG and behavioral arousal for a mean of 131 min. In contrast, morphine challenges in saline control rats produced a biphasic EEG and behavioral response consisting of a mean of 85 min of stupor, followed by a mean of 88 min of arousal. However, at 15 days EKC post-withdrawal, EKC challenges produced a biphasic EEG and behavioral response consisting of a mean of 57 min of depression followed by a mean of 55 min of arousal; control saline rats demonstrated similar responses to EKC challenges. Similar results were obtained at one month post-withdrawal for all groups. Thus, protracted effects on EEG and behavior were evident in rats chronically treated with morphine, but not in rats chronically treated with EKC.
一组六只成年雌性斯普拉格-道利大鼠在八天内接受了一系列自动静脉注射吗啡。同样，另一组六只大鼠接受了乙基酮环唑辛（EKC）。对照大鼠接受慢性静脉注射生理盐水。结果显示对吗啡和EKC的脑电图及行为效应产生了耐受性。在停用吗啡15天后，再次注射吗啡会导致脑电图和行为昏迷，平均持续5分钟，随后脑电图和行为兴奋，平均持续131分钟。相比之下，在生理盐水对照大鼠中再次注射吗啡会产生双相脑电图和行为反应，包括平均85分钟的昏迷，随后是平均88分钟的兴奋。然而，在停用EKC 15天后，再次注射EKC会产生双相脑电图和行为反应，包括平均57分钟的抑制，随后是平均55分钟的兴奋；对照生理盐水大鼠对再次注射EKC表现出类似反应。所有组在停药一个月时都得到了类似结果。因此，长期使用吗啡治疗的大鼠对脑电图和行为有明显的持久影响，但长期使用EKC治疗的大鼠则没有。
