Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer
Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer
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DOI：
10.1016/j.neuroimage.2004.12.023
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发表时间：
2005-08-15
期刊：
影响因子：
5.7
通讯作者：
Chollet, F
中科院分区：
文献类型：
--
作者：
Loubinoux, I;Tombari, D;Chollet, F
SSRIs被认为可以调节运动行为。单剂量的选择性胆碱能再摄取抑制剂（SSRI）如氟西汀、帕罗西汀或氟伏沙明已被证明可改善健康受试者简单感觉运动任务的运动表现和信息处理效率。在皮层水平，单剂量的SSRI显示诱导参与运动的初级感觉运动皮层（S1 M1）的过度激活（Loubinoux，L，Boulanouar，K.，Ranjeva，J. P.，Carel，C.，贝里岛，Rascol，O.，Celsis，P.，和Chollet，F.，1999.单剂量单胺类神经传递增强剂氟西汀和非诺唑酮在手感觉运动任务中调节脑功能磁共振成像激活。J.塞雷布血流代谢19 1365-1375，Loubinoux，I.，Pariente，J.，Boulanouar，K.，Carel，C.，Manelfe，C. Rascol，0.，Celsis，P.，和Chollet，F.，2002.单剂量5-羟色胺神经传递激动剂帕罗西汀增强运动输出。在健康受试者中进行的双盲、安慰剂对照、fMRI研究。NeuroImage 15 26-36）。由于SSRIs通常给药数周，我们评估了一个月的帕罗西汀长期给药对较大群体的行为和大脑的影响。在一项双盲、安慰剂对照和交叉研究中，19名受试者分别接受每日20 mg帕罗西汀或安慰剂，持续30天，间隔3个月的洗脱期。每个阶段结束后，受试者都接受了fMRI（主动或被动运动，灵巧性任务，感觉辨别任务）和行为评估。同时，进行TMS（经颅磁刺激）研究（Gerdelat-Mas，A.，卢比努岛Tombari，D.，Rascol，0.，Chollet，F.，Simonetta-Moreau，M.，2005.长期服用选择性5-羟色胺再摄取抑制剂（SSRI）帕罗西汀可调节健康受试者的运动皮层兴奋性。NeuroImage 27，314-322）。结果如下：一方面，帕罗西汀改善了手指敲击试验的运动表现（P = 0.02），而对选择反应时、力量和灵巧性没有显著影响。受试者在处理刺激和运动反应之间的空间不一致性方面也更快（P = 0.04）。为了区分行为成分，对所有运动测试进行主成分分析，并区分几个特征：力量，速度，技能，注意力和运动反应编码。帕罗西汀能提高运动反应编码效率（因素3的MANOVA，P = 0.01）。另一方面，无论是运动任务还是感觉任务，无论是简单任务还是复杂任务，慢性给药均诱导S1 M1显著活化减退（随机效应分析，P < 0.05）。脑电活动减退与手指敲击实验成绩的改善相关（P < 0.05），提示脑运动加工效率更高。结论：我们的研究结果表明，慢性帕罗西汀给药后，感觉和运动脑激活的明显调制。行为和大脑效率的改善。可以假设，单胺类，通过一种非特异性的作用，可以调整锥体神经元的反应，以优化性能。(c)2004年爱思唯尔公司All rights reserved.
SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, L, Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365-1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, 0., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26-36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, 0., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27, 314-322). Results: On the one hand, paroxetine improved motor performances at the finger tapping test (P = 0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P = 0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P = 0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P < 0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P < 0.05) suggesting more efficiency in cerebral motor processing. Conclusions: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances. (c) 2004 Elsevier Inc. All rights reserved.