Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine-Seeking in a Rat Model

Exercise has shown promise as a treatment for substance use disorders; however, the mechanism underlying its efficacy has remained elusive. Here, we use RNA-sequencing as an unbiased and hypothesis generating approach to explore transcriptional changes in the dorsal medial prefrontal cortex associated with cocaine-craving and the anti-craving effects of exercise. Excitingly, our findings revealed possible glutamatergic mechanisms as well as other novel candidate mechanisms (e.g., circadian rhythm regulation and neuronal survival). These findings provide a rich resource for future studies aimed at manipulating these molecular networks in order to better understand how exercise decreases cocaine-craving.

运动作为物质使用障碍（substance use disorders）的治疗手段已展现出潜力，但其疗效背后的潜在机制仍未明确。本研究采用RNA测序（RNA-sequencing）作为无偏倚的假说生成式研究方法，探究与可卡因渴求（cocaine-craving）相关的背内侧前额叶皮层（dorsal medial prefrontal cortex）的转录变化，以及运动的抗渴求效应。令人振奋的是，本研究结果揭示了潜在的谷氨酸能机制，以及其他全新的候选机制（例如昼夜节律调控与神经元存活）。本研究结果为后续通过调控这些分子网络以深入解析运动如何降低可卡因渴求的相关研究提供了宝贵的研究资源。