Kuo Hsiao-I, Paulus Walter, Batsikadze Giorgi, Jamil Asif, Kuo Min-Fang, Nitsche Michael A
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen, Germany.
Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.
Neuropsychopharmacology. 2016 Apr;41(5):1223-30. doi: 10.1038/npp.2015.270. Epub 2015 Sep 2.
Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.
血清素通过调节长时程增强（LTP）和长时程抑制（LTD）来影响记忆形成。相应地，急性给予选择性血清素再摄取抑制剂（SSRI）可增强经颅直流电刺激（tDCS）在人类中诱导的类似LTP的可塑性。然而，SSRI通常需要一些时间来减轻临床症状，如焦虑、消极情绪以及抑郁和焦虑症的相关症状。这可能与慢性血清素能增强对可塑性的影响至少部分不同于单剂量用药有关。在此，我们在一项部分双盲、安慰剂（PLC）对照、随机交叉研究中，探究了慢性应用SSRI西酞普兰（CIT）对健康人类中tDCS诱导的可塑性的影响。此外，我们通过N-甲基-D-天冬氨酸受体拮抗作用，探究了可塑性诱导对谷氨酸能系统的依赖性。12名健康受试者接受PLC药物治疗，并结合对初级运动皮层进行阳极或阴极tDCS。之后，相同的受试者连续35天服用CIT（20毫克/天）。在此期间，进行了另外四项干预（CIT和PLC药物治疗并结合阳极/阴极tDCS、CIT和右美沙芬（150毫克）并结合阳极/阴极tDCS）。通过经颅磁刺激诱发的运动诱发电位幅度来监测可塑性。慢性应用CIT可增加并延长阳极tDCS诱导的类似LTP的可塑性超过24小时，并将阴极tDCS诱导的类似LTD的可塑性转变为易化作用。这些效应被右美沙芬消除。慢性血清素能增强导致类似LTP的谷氨酸能可塑性增强，这可能部分解释了SSRI在抑郁症和其他神经精神疾病中的治疗作用。
