School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Neuropharmacology. 2024 Jan 1;242:109761. doi: 10.1016/j.neuropharm.2023.109761. Epub 2023 Oct 12.
Animal models indicate that motor behaviour is shaped by monoamine neuromodulators released diffusely throughout the brain and spinal cord. As an alternative to conducting a single study to explore the effects of neuromodulators on the human motor system, we have identified and collated human experiments investigating motor effects of well-characterised drugs that act on serotonergic and noradrenergic networks. In doing so, we present strong neuropharmacology evidence that human motor pathways are affected by neuromodulators across both healthy and clinical populations, insight that cannot be determined from a single reductionist experiment. We have focused our review on the effects that monoaminergic drugs have on muscle responses to non-invasive stimulation of the motor cortex and peripheral nerves, and other closely related tests of motoneuron excitability, and discuss how these measurement techniques elucidate the effects of neuromodulators at motor cortical and spinal motoneuronal levels. Although there is some heterogeneity in study methods, we find drugs acting to enhance extracellular concentrations of serotonin tend to reduce the excitability of the human motor cortex, and enhanced extracellular concentrations of noradrenaline increases motor cortical excitability by enhancing intracortical facilitation and reducing inhibition. Both monoamines tend to enhance the excitability of spinal motoneurons. Overall, this review details the importance of neuromodulators for the output of human motor pathways and suggests that commonly prescribed monoaminergic drugs target the motor system in addition to their typical psychiatric/neurological indications.
动物模型表明，运动行为是由脑和脊髓中弥散释放的单胺类神经调质塑造的。作为替代单一研究探索神经调质对人类运动系统影响的方法，我们已经确定并整理了人类实验，这些实验研究了作用于 5-羟色胺能和去甲肾上腺素能网络的特征明确药物对运动的影响。这样做，我们提供了强有力的神经药理学证据，证明人类运动通路受到神经调质的影响，无论是在健康人群还是临床人群中，这种洞察力都无法从单一的还原论实验中确定。我们的综述重点关注单胺类药物对肌肉对外周神经和运动皮层非侵入性刺激的反应的影响，以及其他密切相关的运动神经元兴奋性测试，并讨论这些测量技术如何阐明神经调质在运动皮层和脊髓运动神经元水平的作用。尽管研究方法存在一定的异质性，但我们发现，增加 5-羟色胺细胞外浓度的药物往往会降低人类运动皮层的兴奋性，而增加去甲肾上腺素细胞外浓度则通过增强皮质内易化和减少抑制来增加运动皮层的兴奋性。两种单胺类药物都倾向于增强脊髓运动神经元的兴奋性。总的来说，本综述详细说明了神经调质对人类运动通路输出的重要性，并表明常用的单胺类药物除了其典型的精神科/神经科适应证外，还靶向运动系统。
