Gerdelat-Mas A, Loubinoux I, Tombari D, Rascol O, Chollet F, Simonetta-Moreau M
Inserm U 455, Toulouse, France.
Neuroimage. 2005 Aug 15;27(2):314-22. doi: 10.1016/j.neuroimage.2005.05.009.
The aim of the study was to investigate the effect of chronic administration of paroxetine (selective serotonin reuptake inhibitor: SSRI) on motor cortex excitability in healthy subjects by means of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and behavioral motor tests. In a randomized, double-blind, crossover study, twenty-one right-handed subjects received 20 mg daily of either paroxetine or a placebo over a period of 30 days separated by a period of 3 months wash-out. The TMS study is presented here correlated with some results of the motor behavior study (finger tapping test) and the fMRI study (primary sensorimotor cortex (S1M1) volume of activation). TMS was used to test motor threshold (MT), motor evoked potential recruitment curve (RC), cortical silent period (CSP) and paired-pulse intracortical inhibition and facilitation (ICI, ICF). Chronic administration of paroxetine did not modulate ICI or CSP but induced a significant enhancement of mean ICF (ANOVA P=0.04), which significantly correlated with increase of speed in a finger tapping test (P=0.02). This suggests a modulation of cortical interneuronal excitatory pathways without changes in the excitability of cortical inhibitory GABAergic interneurons. A decrease of RC (ANOVA P=0.05) was also observed after 30 days intake of paroxetine in comparison with placebo and was associated with changes of fMRI activation intensity (left S1M1 hypoactivation, ), without changes of S1M1 activation volume. Finally, the different modulation of RC and ICF after chronic administration of paroxetine compared to single dose (opposite effects) emphasizes the different pharmacological action of the drug at cortical level depending on its acute or long-term administration.
本研究的目的是通过经颅磁刺激（TMS）、功能磁共振成像（fMRI）和行为运动测试，研究慢性给予帕罗西汀（选择性5-羟色胺再摄取抑制剂：SSRI）对健康受试者运动皮层兴奋性的影响。在一项随机、双盲、交叉研究中，21名右利手受试者在30天内每日服用20mg帕罗西汀或安慰剂，中间间隔3个月的洗脱期。本文呈现的TMS研究结果与运动行为研究（手指敲击测试）和fMRI研究（初级感觉运动皮层（S1M1）激活体积）的一些结果相关。TMS用于测试运动阈值（MT）、运动诱发电位募集曲线（RC）、皮层静息期（CSP）以及配对脉冲皮质内抑制和易化（ICI、ICF）。慢性给予帕罗西汀并未调节ICI或CSP，但导致平均ICF显著增强（方差分析P=0.04），这与手指敲击测试中速度的增加显著相关（P=0.02）。这表明皮层中间神经元兴奋性通路发生了调节，而皮层抑制性GABA能中间神经元的兴奋性没有变化。与安慰剂相比服用帕罗西汀30天后还观察到RC降低（方差分析P=0.05），并且与fMRI激活强度的变化相关（左侧S1M1激活减弱），而S1M1激活体积没有变化。最后，与单次给药相比（作用相反），慢性给予帕罗西汀后RC和ICF的不同调节强调了该药物在皮层水平的药理作用因急性或长期给药而异。
