Effects of Serotonergic Medications on Locomotor Performance in Humans with Incomplete Spinal Cord Injury
Effects of Serotonergic Medications on Locomotor Performance in Humans with Incomplete Spinal Cord Injury
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DOI：
10.1089/neu.2013.3206
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发表时间：
2014-08-01
影响因子：
4.2
通讯作者：
Hornby, T. George
中科院分区：
文献类型：
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作者：
Leech, Kristan A.;Kinnaird, Catherine R.;Hornby, T. George
不完全性脊髓损伤（iSCI）通常会导致显著的运动障碍，从而导致功能活动性降低。脊髓回路的下行多巴胺能（5 HT）输入的丧失被认为有助于运动障碍，通过增强5 HT信号传导来增强运动功能。然而，SCI中痉挛性运动行为的存在部分归因于脊髓5 HT受体的变化，其在缺乏5 HT的情况下增强其活性，尽管证明使这些受体失活的5 HT药剂的运动效应的数据是相互矛盾的。增强或抑制5 HT信号传导对运动功能的影响尚未在人类iSCI中进行彻底评估。因此，本研究的目的是研究5 HT药物对10名慢性（>1年）iSCI受试者运动的急性影响。采用双盲、随机、交叉设计，在单剂量给予选择性5-羟色胺再摄取抑制剂（SSRI）或5-HT拮抗剂之前和之后，评估地上和跑步机运动性能峰值，包括步态运动学、肌电图（EMG）活动和耗氧量。结果表明，两种药物均未导致运动改善，在5 HT拮抗剂后观察到地上步态速度峰值显著降低（从0.8 +/- 0.1 m/s降至0.7 +/- 0.1 m/s; p = 0.01）。此外，5-HT药物对EMG活动有不同的影响，5-HT拮抗剂降低伸肌活动，SSRI增加屈肌活动。因此，我们的数据表明，急性操纵5 HT信号，尽管肌肉活动的变化，并没有改善运动性能后iSCI。
Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. The effects of enhancement or depression of 5HT signaling on locomotor function have not been thoroughly evaluated in human iSCI. Therefore, the aim of the current study was to investigate acute effects of 5HT medications on locomotion in 10 subjects with chronic (>1 year) iSCI. Peak overground and treadmill locomotor performance, including measures of gait kinematics, electromyographic (EMG) activity, and oxygen consumption, were assessed before and after single-dose administration of either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using a double-blinded, randomized, cross-over design. Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8 +/- 0.1 to 0.7 +/- 0.1 m/s; p = 0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI.