Koyuncuoğlu H, Aricioğlu F
Department of Pharmacology and Clinical Pharmacology, Istanbul Medical Faculty, Turkey.
Pharmacol Biochem Behav. 1993 Apr;44(4):939-41. doi: 10.1016/0091-3057(93)90028-r.
Pregnant rats were SC injected with physiological saline (control) or 10 mg/kg morphine (morphine group) or 2 mg/kg naloxone (naloxone group) three times daily during the last 5 days of gestation. Three weeks after birth, male young rats of each group were taken and placed in separate cages. When their body weight reached 130-150 g, 10 rats from control, morphine, and naloxone groups were SC implanted with two pellets containing 75 mg morphine base (total 150 mg). Three days following implantation, rats were IP given 2 mg/kg naloxone for precipitated abstinence syndrome. Immediately after naloxone injection, rats were strictly observed for 15 min and jumping, wet-dog shakes, teeth-chattering, diarrhoea, defecation, and ptosis counted or rated. All abstinence syndrome signs were significantly higher in the morphine or naloxone group than in control. On the basis of the previous experimental findings supporting the idea that opiate physical dependence is related to the binding of opiate, possibly other than their own, to NMDA receptors and the upregulation and/or supersensitivity associated with the binding, the intensification of morphine dependence has been attributed to the long-lasting NMDA receptor upregulation and/or supersensitivity.
在妊娠的最后5天，对怀孕大鼠每日皮下注射3次生理盐水（对照组）、10毫克/千克吗啡（吗啡组）或2毫克/千克纳洛酮（纳洛酮组）。出生3周后，选取每组的雄性幼鼠并单独饲养在笼子里。当它们的体重达到130 - 150克时，从对照组、吗啡组和纳洛酮组中各选取10只大鼠，皮下植入两颗含75毫克吗啡碱的药丸（共150毫克）。植入后3天，给大鼠腹腔注射2毫克/千克纳洛酮以引发戒断综合征。纳洛酮注射后立即对大鼠进行15分钟的严格观察，并对跳跃、湿狗样抖动、牙齿打颤、腹泻、排便和眼睑下垂进行计数或评分。吗啡组或纳洛酮组的所有戒断综合征体征均显著高于对照组。基于先前的实验结果支持阿片类物质身体依赖性与阿片类物质（可能不是其自身）与NMDA受体的结合以及与该结合相关的上调和/或超敏反应有关的观点，吗啡依赖性的增强归因于持久的NMDA受体上调和/或超敏反应。
