College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Korea.
Int J Mol Sci. 2021 Jul 30;22(15):8203. doi: 10.3390/ijms22158203.
Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3β expression. However, the phosphorylation levels of Ser9-GSK-3β were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3β activation by the regulation of the striatal glutamate signaling pathway.
体育锻炼可减少药物成瘾者在药物起始阶段、长期成瘾、戒断和复发期间使用药物的程度、持续时间和频率。然而，关于运动引起的神经生物学变化的信息有限。本研究旨在探讨强制适度耐力运动训练对甲基苯丙胺（METH）诱导的行为及相关神经生物学变化的影响。雄性 Sprague Dawley 大鼠接受 METH（1 mg/kg/天，腹腔注射）和/或强制适度耐力运动（跑步机跑步，21 m/min，每天 60 分钟）治疗 2 周。在这两周内，耐力运动训练显著减少了 METH 诱导的过度活动。METH 和/或运动处理增加了纹状体多巴胺（DA）水平，降低了 p（Thr308）-Akt 表达，增加了 p（Tyr216）-GSK-3β表达。然而，运动组 Ser9-GSK-3β 的磷酸化水平显著增加。METH 给药显著增加了纹状体中 NMDAr1、CaMKK2、MAPKs 和 PP1 的表达，运动处理显著降低了这些分子的表达。因此，耐力运动通过调节纹状体谷氨酸信号通路抑制了 GSK-3β 的激活，从而抑制了 METH 诱导的过度活动。
