Qian Hongyan, Xi Zhijia, Liang Min, An Ran, Gao Baoyao, Chen Xingyao, Liu Zijun, Shang Qing, Chen Gang, Xiao Lei, Liu Xinshe
Institute of Forensic Injury, Institute of Forensic Bioevidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Neurochem Res. 2025 Mar 17;50(2):120. doi: 10.1007/s11064-025-04368-0.
Methamphetamine (METH) addiction is a chronic brain disorder characterized by intense drug cravings and high relapse rates. Traditional Chinese medicines (TCM) have shown efficacy in treating METH addiction via TrkB/ERK signaling. However, the role of Polygalae Radix (PR), a neuropharmacological active TCM, in METH addiction remains unclear. This study examined the effects of PR (25, 50, and 100 mg/kg) on locomotor activity in mice and its impact on METH-induced behavioral sensitization (BS) at different stages. Western blotting (WB) assessed TrkB and ERK expression across brain regions. PR (25 and 50 mg/kg) alone had no effect on locomotor activity in mice, whereas 100 mg/kg significantly reduced locomotor activity. PR (25 and 50 mg/kg) administered during the development phase inhibited METH-induced locomotor activity, but its administration during the expression phase had no impact. Continuous PR (25 and 50 mg/kg) administration throughout the entire process prevented METH-induced BS in mice. WB analysis revealed that PR alone elevated ERK in the prefrontal cortex, nucleus accumbens (NAc), caudate putamen (CPu), and TrkB in the CPu. During the development phase, PR inhibited METH-induced TrkB/ERK increases in the CPu, whereas, during the expression phase, ERK elevation in the CPu was mitigated. Continuous PR administration blocked METH-induced TrkB/ERK increases in the CPu and ERK levels in the NAc. These findings indicate that PR attenuates METH-induced BS and locomotor activity during the developmental phase through the TrkB/ERK pathway in the CPu, highlighting its therapeutic potential for METH addiction.
甲基苯丙胺（METH）成瘾是一种慢性脑部疾病，其特征为强烈的药物渴望和高复发率。传统中药（TCM）已显示出通过TrkB/ERK信号通路治疗METH成瘾的功效。然而，远志（PR）这种具有神经药理学活性的中药在METH成瘾中的作用仍不清楚。本研究考察了PR（25、50和100mg/kg）对小鼠运动活动的影响及其在不同阶段对METH诱导的行为敏化（BS）的影响。蛋白质免疫印迹法（WB）评估了大脑各区域TrkB和ERK的表达。单独使用PR（25和50mg/kg）对小鼠运动活动没有影响，而100mg/kg则显著降低了运动活动。在发展阶段给予PR（25和50mg/kg）可抑制METH诱导的运动活动，但在表达阶段给予则没有影响。在整个过程中持续给予PR（25和50mg/kg）可预防METH诱导的小鼠BS。WB分析显示，单独使用PR可使前额叶皮质、伏隔核（NAc）、尾状壳核（CPu）中的ERK升高，使CPu中的TrkB升高。在发展阶段，PR抑制了METH诱导的CPu中TrkB/ERK的增加，而在表达阶段，CPu中ERK的升高得到缓解。持续给予PR可阻断METH诱导的CPu中TrkB/ERK的增加以及NAc中ERK水平的升高。这些发现表明，PR在发展阶段通过CPu中的TrkB/ERK途径减轻了METH诱导的BS和运动活动，突出了其对METH成瘾的治疗潜力。
