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跑步机运动对接受美沙酮维持治疗的吗啡戒断大鼠美沙酮戒断诱导的运动敏化及腹侧苍白球和腹侧被盖区脑源性神经营养因子水平的影响。

Effects of treadmill exercise on methadone withdrawal-induced locomotor sensitization and the ventral pallidum and ventral tegmental area BDNF levels in morphine withdrawn rats receiving methadone maintenance treatment.

作者信息

Alizadeh Maryam, Zahedi-Khorasani Mahdi, Bandegi Ahmad-Reza, Yousefi Behpour, Rashidy-Pour Ali, Sameni Hamid Reza, Miladi-Gorji Hossein

机构信息

Laboratory of Animal Addiction Models, Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Student Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Laboratory of Animal Addiction Models, Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

Neurosci Lett. 2018 Sep 14;683:33-37. doi: 10.1016/j.neulet.2018.06.037. Epub 2018 Jun 21.

Abstract

This study examined the effects of treadmill exercise on the methadone withdrawal -induced locomotor sensitization, the ventral tegmental area (VTA) and ventral pallidum (VP) BDNF levels in morphine withdrawn rats receiving methadone maintenance treatment (MMT). The rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. The exercising rats receiving MMT were forced to run on a motorized treadmill for 30 days during morphine withdrawal. Then, rats were exposed to a 14-day methadone withdrawal period, without any exercise and then challenged with morphine (1 mg/kg, ip) and evaluated for locomotor activity. Also, the VTA-VP BDNF levels were assessed before and after receiving MMT. The sedentary morphine-dependent rats receiving MMT and morphine-dependent rats receiving saline challenged to morphine exhibited a higher level of locomotor activity compared to Sal/Sal/Sed group after withdrawal of drug. While, the level of locomotor activity was lower in the D/Meth/Sed than in D/Sal/Sed rats. The VP BDNF level and the locomotors response were higher and lower, respectively in the D/Meth/Sed and D/Sal/Exc than the D/Sal/Sed rats. Exercise had no effect on the locomotors response and the VP BDNF levels in morphine-dependent rats receiving MMT. Our results showed that the sedentary morphine-dependent rats challenged to morphine enhanced the morphine-induced hyperlocomotion, whereas decreased the VP BDNF levels. MMT resulted in a persistent of locomotor sensitization caused by morphine withdrawal, though milder. Exercise had no effect on the locomotors response and the VTA-VP BDNF levels in the D/Meth/Exc.

摘要

本研究考察了跑步机运动对接受美沙酮维持治疗(MMT)的吗啡戒断大鼠的美沙酮戒断诱导的运动敏化、腹侧被盖区(VTA)和腹侧苍白球(VP)脑源性神经营养因子(BDNF)水平的影响。大鼠每天分两次(间隔12小时,剂量为10mg/kg)接受吗啡慢性治疗14天。接受MMT的运动大鼠在吗啡戒断期间被迫在电动跑步机上跑步30天。然后,大鼠经历14天的美沙酮戒断期,期间不进行任何运动,之后用吗啡(1mg/kg,腹腔注射)进行激发,并评估其运动活性。此外,在接受MMT前后评估VTA-VP BDNF水平。与撤药后的Sal/Sal/Sed组相比,接受MMT的久坐不动的吗啡依赖大鼠和接受生理盐水并经吗啡激发的吗啡依赖大鼠表现出更高水平的运动活性。而D/Meth/Sed组的运动活性水平低于D/Sal/Sed组大鼠。与D/Sal/Sed组大鼠相比,D/Meth/Sed组的VP BDNF水平较高,而运动反应较低,D/Meth/Sed组和D/Sal/Exc组的运动反应和VP BDNF水平则分别较低和较高。运动对接受MMT的吗啡依赖大鼠的运动反应和VP BDNF水平没有影响。我们的结果表明,接受吗啡激发的久坐不动的吗啡依赖大鼠增强了吗啡诱导的运动亢进,而降低了VP BDNF水平。MMT导致了由吗啡戒断引起的运动敏化的持续存在,尽管程度较轻。运动对D/Meth/Exc组的运动反应和VTA-VP BDNF水平没有影响。

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