Motaghinejad Majid, Fatima Sulail, Banifazl Sanaz, Bangash Mohammad Yasan, Karimian Morteza
Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Physiology, Tehran University of Medical Sciences, International Campus, Tehran, Iran.
Adv Biomed Res. 2016 Nov 28;5:178. doi: 10.4103/2277-9175.188491. eCollection 2016.
Morphine dependency usually results in undesired outcomes such as anxiety, depression, and cognitive alterations. In this study, morphine was used to manage morphine dependence-induced anxiety, depression, and learning and memory disturbances.
Forty rats were divided equally into five groups. Group 1 received saline for 21 days. Groups 2-5 were dependent by increasing administration of morphine (15-45 mg/kg) for 7 days. For the next 14 days, morphine was administered as the following regimen: Group 2: once daily; 45 mg/kg (positive controls), Group 3: the same dose with an increasing interval (6 h longer than the previous intervals each time), Group 4: the same dose with an irregular intervals (12, 24, 36 h intervals interchangeably), and Group 5: decreasing doses once daily (every time 2.5 mg/kg less than the former dosage). On days 22-26, elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were performed to investigate anxiety level and depression in animals. Between 17 and 21 days, Morris water maze (MWM) was used to evaluate the spatial learning and memory.
Chronic morphine administration caused depression and anxiety as observed by FST, EPM, and TST and decreased motor activity in OFT and caused impairment in learning and memory performance in MWM. Treatment with our protocol as increasing interval, irregular interval, and decreasing dosage of morphine caused marked reduction in depression, anxiety, and improved cognition performance compared with positive control group; and attenuated motor deficits in morphine-dependent rats, remarkably.
Change in dosage regimens of morphine can reduce morphine-induced anxiety, depression, and cognitive impairments.
吗啡依赖通常会导致诸如焦虑、抑郁和认知改变等不良后果。在本研究中，使用吗啡来处理吗啡依赖引起的焦虑、抑郁以及学习和记忆障碍。
40只大鼠平均分为五组。第1组给予生理盐水，持续21天。第2 - 5组通过增加吗啡剂量（15 - 45毫克/千克）给药7天使其产生依赖。在接下来的14天里，按以下方案给予吗啡：第2组：每日一次；45毫克/千克（阳性对照组），第3组：相同剂量但给药间隔逐渐增加（每次比前一次间隔长6小时），第4组：相同剂量但给药间隔不规律（12、24、36小时间隔交替），第5组：每日一次递减剂量（每次比前一剂量少2.5毫克/千克）。在第22 - 26天，进行高架十字迷宫（EPM）、旷场试验（OFT）、强迫游泳试验（FST）和悬尾试验（TST）以研究动物的焦虑水平和抑郁情况。在第17 - 21天，使用莫里斯水迷宫（MWM）评估空间学习和记忆能力。
通过FST、EPM和TST观察到，慢性给予吗啡会导致抑郁和焦虑，并降低OFT中的运动活性，且在MWM中导致学习和记忆表现受损。与阳性对照组相比，采用我们的方案，即增加给药间隔、不规律给药间隔和递减吗啡剂量进行治疗，可显著减轻抑郁、焦虑并改善认知表现；并且明显减轻了吗啡依赖大鼠的运动功能缺陷。
吗啡给药方案的改变可减轻吗啡引起的焦虑、抑郁和认知障碍。
