L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats
L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats
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DOI：
10.1016/j.bbr.2003.12.021
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发表时间：
2004-08-31
影响因子：
2.7
通讯作者：
Schmidt, WJ
中科院分区：
文献类型：
--
作者：
Alam, M;Schmidt, WJ
外周和局部给药鱼藤酮（线粒体复合体1的抑制剂）已被提出作为帕金森病（PD）的模型，因为它诱导与α -突触核蛋白包涵体相关的黑质纹状体变性。如果鱼藤酮引起的症状是帕金森病的一种模型，那么左旋多巴就可以抵消这些症状。为了回答这个问题，我们给大鼠注射2.5 mg/kg的鱼藤酮48天。行为学数据显示，与对照组相比，鱼藤酮组动物的猝倒症状明显增加，运动活动减少，生化数据显示纹状体（Cpu）和黑质中多巴胺水平显著降低。为了研究左旋多巴对大鼠运动障碍的逆转作用，在鱼藤酮治疗的大鼠中，每天给予10 mg/kg的左旋多巴与外周氨基酸脱羧酶抑制剂苯塞拉肼联合腹腔注射，持续10天。这种治疗抵消了麻痹，增加了运动活动和次数，但减少了不活动的坐着。在该动物模型（鱼藤酮模型）中，麻痹试验和运动活动显示临床使用的抗帕金森药物左旋多巴替代鱼藤酮引起多巴胺（DA）缺乏症。(C) 2004 Elsevier B.V.版权所有
Peripherally and locally administered rotenone (an inhibitor of mitochondrial complex 1) has been proposed as a model of Parkinson's disease (PD) as it induces nigrostriatal degeneration associated with alpha-synuclein inclusions. If rotenone-induced symptoms represent a model of PD, than they should be counteracted by L-DOPA. To answer this question, rats were treated with rotenone 2.5 mg/kg over 48 days. Behavioural data showed a strong increase in catalepsy, a decrease in locomotor activity and biochemical data showed a significant depletion of dopamine levels in the striatum (Cpu) and substantia nigra in rotenone treated animals compared to vehicle. To examine the effectiveness Of L-DOPA in reversing the motor deficit in rats, a dose Of L-DOPA (10 mg/kg) in combination with the peripheral amino acid decarboxylase inhibitor benserazide were daily administrated intraperitonially for a period of 10 days in the rotenone-treated rats. This treatment counteracted catalepsy and increased locomotor activity and number of rearings but decreased inactive sitting. In this animal model (rotenone model), catalepsy tests and motor activities showed that the clinically used anti-parkinsonian drug L-DOPA substitutes rotenone-induced dopamine (DA) deficiency. (C) 2004 Elsevier B.V. All rights reserved.