Tan Liang, Ge Hongfei, Tang Jun, Fu Chuhua, Duanmu Wangsheng, Chen Yujie, Hu Rong, Sui Jianfeng, Liu Xin, Feng Hua
Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Experimental Center of Basic Medicine, College of Basic Medical Science, Third Military Medical University, Chongqing 400038, China.
Behav Brain Res. 2015 Feb 15;279:274-82. doi: 10.1016/j.bbr.2014.10.037. Epub 2014 Nov 20.
Traumatic brain injury (TBI) often results in multiple neuropsychiatric sequelae, including cognitive, emotional, and behavioral problems. Among them, depression is a common psychiatric symptom, and links to poorer recovery. Amantadine, as an antiparkinsonian, increases dopamine release, and blocks dopamine reuptake, but has recently received attention for its effectiveness as an antidepressant. In the present study, we first induced a post-TBI depression rat model to probe the efficacy of amantadine therapy in reducing post-TBI depression. The DA concentration in the striatum of the injured rats, as well as the degeneration and apoptosis of dopaminergic neurons in the substantia nigra (SN), were checked along with the depression-like behavior. The results showed that amantadine therapy could significantly ameliorate the depression-like behavior, improving the DA level in the striatum and decreasing the degeneration and apoptosis of dopaminergic neurons in the SN. The results indicated that the anti-depression effect may result from the increase of extracellular DA concentration in the striatum and/or the indirect neuroprotection on the dopaminergic neurons in the SN. We conclude that DA plays a critical role in post-TBI depression, and that amantadine shows its potential value in anti-depression treatment for TBI.
创伤性脑损伤（TBI）常导致多种神经精神后遗症，包括认知、情感和行为问题。其中，抑郁是一种常见的精神症状，且与较差的恢复情况相关。金刚烷胺作为一种抗帕金森药物，可增加多巴胺释放并阻断多巴胺再摄取，但最近因其作为抗抑郁药的有效性而受到关注。在本研究中，我们首先诱导了创伤性脑损伤后抑郁大鼠模型，以探究金刚烷胺治疗对减轻创伤性脑损伤后抑郁的疗效。同时检测了损伤大鼠纹状体中的多巴胺浓度，以及黑质（SN）中多巴胺能神经元的变性和凋亡情况，并观察了抑郁样行为。结果表明，金刚烷胺治疗可显著改善抑郁样行为，提高纹状体中的多巴胺水平，并减少黑质中多巴胺能神经元的变性和凋亡。结果表明，抗抑郁作用可能源于纹状体细胞外多巴胺浓度的增加和/或对黑质中多巴胺能神经元的间接神经保护作用。我们得出结论，多巴胺在创伤性脑损伤后抑郁中起关键作用，且金刚烷胺在创伤性脑损伤的抗抑郁治疗中显示出其潜在价值。
