Key Laboratory of Central CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Psychiatry. 2021 Nov;26(11):6187-6197. doi: 10.1038/s41380-021-01336-2. Epub 2021 Oct 22.
Drug exposure impairs cortical plasticity and motor learning, which underlies the reduced behavioral flexibility in drug addiction. Physical exercise has been used to prevent relapse in drug rehabilitation program. However, the potential benefits and molecular mechanisms of physical exercise on drug-evoked motor-cortical dysfunctions are unknown. Here we report that 1-week treadmill training restores cocaine-induced synaptic deficits, in the form of improved in vivo spine formation, synaptic transmission, and spontaneous activities of cortical pyramidal neurons, as well as motor-learning ability. The synaptic and behavioral benefits relied on de novo protein synthesis, which are directed by the activation of the mechanistic target of rapamycin (mTOR)-ribosomal protein S6 pathway. These findings establish synaptic functional restoration and mTOR signaling as the critical mechanism supporting physical exercise training in rehabilitating the addicted brain.
药物暴露会损害皮质可塑性和运动学习，这是药物成瘾导致行为灵活性降低的基础。运动已被用于预防药物康复计划中的复发。然而，运动对药物引起的运动皮层功能障碍的潜在益处和分子机制尚不清楚。在这里，我们报告了为期一周的跑步机训练恢复了可卡因引起的突触缺陷，表现为体内棘突形成、突触传递和皮质锥体神经元自发活动的改善，以及运动学习能力的提高。这种突触和行为的改善依赖于新蛋白质的合成，这是由雷帕霉素靶蛋白（mTOR）-核糖体蛋白 S6 通路的激活所指导的。这些发现确立了突触功能的恢复和 mTOR 信号作为支持运动训练在康复成瘾大脑方面的关键机制。
