Partial dopamine depletion in MPTP-treated mice differentially altered motor skill learning and action control
Partial dopamine depletion in MPTP-treated mice differentially altered motor skill learning and action control
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DOI：
10.1016/j.bbr.2011.11.019
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发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Cyr, Michel
中科院分区：
文献类型：
--
作者：
Chagniel, Laure;Robitaille, Christine;Cyr, Michel
最近的研究结果表明，神经递质多巴胺（DA）系统在运动控制和习惯和技能的获得中发挥作用。然而，从运动表现中分离DA介导的运动学习仍然具有挑战性，因为大多数研究通常包括严重DA耗尽的小鼠。用神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）研究了DA耗竭对小鼠加速转棒、悬丝和杆三种运动行为的影响。进行三种方案以不同程度地减少DA合成：4次注射（i. p.）9 mg/kg，1天; 4次注射（i. p.）或5次注射（s.c.）30 mg/kg，持续5天。DA耗竭的严重程度通过使用蛋白质印迹技术评价纹状体中的酪氨酸羟化酶（TH）和多巴胺转运蛋白水平来评估。根据小鼠TH水平分为轻度、中度、显著和重度四组。在这些小鼠中，一般的运动能力，如协调，运动速度和肌肉力量是相对完整的，而受损的收购熟练的行为发生在小鼠中的TH水平显着和严重的减少。标记的和严重DA耗尽的小鼠在第一个训练日的第一次试验中表现出较低的分数，并且在接下来的几天中在加速旋转棒上表现出更慢的进展。基于这些结果，我们的结论是，学习一个熟练的行为是更容易受到DA耗竭比DA介导的控制运动活动。(C)2011 Elsevier B. V.保留所有权利。
Recent findings suggest that the neurotransmitter dopamine (DA) system plays a role in motor control and the acquisition of habits and skills. However, isolating DA-mediated motor learning from motor performance remains challenging as most studies include often severely DA-depleted mice. Using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we investigated the effect of various degrees of DA-depletion in mice on three tests of motor behaviors: the accelerating rotarod, wire suspension and pole tests. Three protocols were performed to decrease DA synthesis to various extents: 4 injections (i.p.) of 9 mg/kg in 1 day; 4 injections (i.p.) of 15 mg/kg in 1 day; or 5 injections (s.c.) of 30 mg/kg in 5 days. Severity of DA-depletion was assessed by the evaluation of tyrosine hydroxylase (TH) and dopamine transporter levels in the striatum using the Western blot technique. Mice were gathered into four different groups according their TH levels: mild, moderate, marked and severe. In these mice, the general motor abilities such as coordination, motion speed and muscular strength were relatively intact whereas impaired acquisition of skilled behavior occurred in mice with marked and severe reduction in TH levels. Marked and severely DA-depleted mice exhibited lower scores within the first trials of the first training day as well as a much slower progression in the following days on the accelerating rotarod. Based on these results, we conclude that the learning of a skilled behavior is more vulnerable to DA depletion than the DA-mediated control of motor activity. (C) 2011 Elsevier B.V. All rights reserved.