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，这是药物成瘾行为灵活性降低的基础。体育锻炼已被用于预防药物康复计划中的复发。然而，体育锻炼对药物诱发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 1 周的跑步机训练以改善体内脊柱形成、突触传递和皮质锥体神经元的自发活动以及运动学习能力的形式恢复了可卡因诱导的突触缺陷。突触和行为益处依赖于从头开始蛋白质合成，这是由雷帕霉素 (mTOR)-核糖体蛋白 S6 通路的机制靶点的激活所指导的。这些发现确立了突触功能恢复和 mTOR 信号转导是支持体育锻炼训练恢复成瘾大脑的关键机制。