Background The serotonergic system has an important impact on basic physiological and higher brain functions. Acute and chronic enhancement of serotonin levels via selective serotonin reuptake inhibitor administration impacts neuroplasticity in humans, as shown by its effects on cortical excitability alterations induced by non-invasive brain stimulation, including transcranial direct current stimulation (tDCS). Nevertheless, the interaction between serotonin activation and neuroplasticity is not fully understood, particularly considering dose-dependent effects. Our goal was to explore dosage-dependent effects of acute serotonin enhancement on stimulation-induced plasticity in healthy individuals. Methods Twelve healthy adults participated in 7 sessions conducted in a crossover, partially double-blinded, randomized, and sham-controlled study design. Anodal and cathodal tDCS was applied to the motor cortex under selective serotonin reuptake inhibitor (20 mg/40 mg citalopram) or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation. Results Under placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for approximately 60–120 minutes after the intervention. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS regardless of the dosage while turning cathodal tDCS-induced excitability diminution into facilitation. For the latter, prolonged effects were observed when 40 mg was administrated. Conclusions Acute serotonin enhancement modulates tDCS after-effects and has largely similar modulatory effects on motor cortex neuroplasticity regardless of the specific dosage. A minor dosage-dependent effect was observed only for cathodal tDCS. The present findings support the concept of boosting the neuroplastic effects of anodal tDCS by serotonergic enhancement, a potential clinical approach for the treatment of neurological and psychiatric disorders.

中文翻译：

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急性血清素增强对经颅直流电刺激效果的剂量依赖性影响

背景 5-羟色胺能系统对基本生理和高级脑功能具有重要影响。通过选择性5-羟色胺再摄取抑制剂给药来急性和慢性增强5-羟色胺水平会影响人类的神经可塑性，如其对非侵入性脑刺激（包括经颅直流电刺激（tDCS））诱导的皮质兴奋性改变的影响所示。然而，血清素激活和神经可塑性之间的相互作用尚不完全清楚，特别是考虑到剂量依赖性效应。我们的目标是探索急性血清素增强对健康个体刺激诱导的可塑性的剂量依赖性影响。方法 12 名健康成人参加了 7 次交叉、部分双盲、随机和假对照研究设计。在选择性血清素再摄取抑制剂（20 mg/40 mg 西酞普兰）或安慰剂药物下，将阳极和阴极 tDCS 应用于运动皮层。通过单脉冲经颅磁刺激监测运动皮层兴奋性。结果 在安慰剂药物治疗下，干预后约 60-120 分钟，阳极 tDCS 增强，阴极 tDCS 降低，兴奋性。无论剂量如何，西酞普兰都能增强和延长阳极 tDCS 诱导的促进作用，同时将阴极 tDCS 诱导的兴奋性降低转化为促进作用。对于后者，当给予 40 mg 时观察到延长的效果。结论 急性 5-羟色胺增强可调节 tDCS 后效，并且无论具体剂量如何，对运动皮层神经可塑性的调节作用都非常相似。仅对阴极 tDCS 观察到较小的剂量依赖性效应。目前的研究结果支持通过 5-羟色胺能增强来增强阳极 tDCS 的神经可塑性效应的概念，这是一种治疗神经和精神疾病的潜在临床方法。