Mokhtari-Zaer Amin, Ghodrati-Jaldbakhan Shahrbanoo, Vafaei Abbas Ali, Miladi-Gorji Hossein, Akhavan Maziar M, Bandegi Ahmad Reza, Rashidy-Pour Ali
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Skin Research Center, Laboratory of Protein and Enzyme, ShahidBeheshti University (M.C.), Shohada-e Tajrish Hospital, Shahrdari St., 1989934148 Tehran, Iran.
Behav Brain Res. 2014 Sep 1;271:160-70. doi: 10.1016/j.bbr.2014.05.061. Epub 2014 Jun 4.
Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals.
长期接触吗啡会导致认知缺陷以及海马体中凋亡蛋白的改变，进而促进细胞死亡，海马体是大脑中对学习和记忆至关重要的区域。体育活动已被证明对大脑健康有益。在当前的研究中，我们研究了自愿运动和跑步机运动对吗啡依赖大鼠的自发戒断症状、相关认知缺陷以及凋亡蛋白变化的影响。通过每日两次注射吗啡（10mg/kg），持续10天来诱导吗啡依赖。然后，将大鼠置于两种不同的运动方案下进行训练：轻度跑步机运动或自愿轮转运动，持续10天。运动训练后，分别通过水迷宫和抑制性回避任务来检测它们的空间学习和记忆以及厌恶记忆。通过免疫印迹法测定海马体中促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的表达。我们发现，长期接触吗啡会损害空间和厌恶记忆，并显著抑制Bcl-2的表达，但Bax的表达保持不变。自愿运动和跑步机运动都减轻了记忆损伤，增加了Bcl-2蛋白的表达，并且只有跑步机运动抑制了吗啡依赖动物中Bax蛋白的表达。此外，两种运动方案都减少了自发吗啡戒断症状的发生。我们的研究结果表明，运动可减少自发吗啡戒断症状，并阻止相关的认知功能损害，还能克服吗啡诱导的凋亡蛋白变化，从而有利于细胞存活。因此，运动可能是一种治疗成瘾个体认知和行为缺陷的有效策略。
