Fluoxetine facilitates use-dependent excitability of human primary motor cortex

Objectives: In poststroke patients, fluoxetine, a selective serotonin-reuptake inhibitor, as an adjunct to physical therapy provided a better functional recovery from motor deficits. The aim of this study was to investigate the effect of a single dose of 20 mg fluoxetine on motor learning and associated cortical changes in healthy right-handed subjects in order to get deeper insight into its facilitating influence on human motor cortex. Methods: Subjects performed a motor task consisting of a simultaneous co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle with and without fluoxetine in a placebo-controlled double-blinded crossover study design. Immediately before and after motor learning motor output maps of the APB muscle were assessed in order to get insight into plastic changes of the muscle representation. Results: We found a significantly improved motor performance under both conditions without having substantial differences between placebo and fluoxetine. After the completion of the motor task there was a medial shift of the APB muscle motor output map. Only after the administration of fluoxetine the sum of MEP amplitudes (SOA) increased and the motor output map enlarged. Conclusions: These findings provide evidence for a use-dependent facilitating effect of fluoxetine on cortical excitability but not on motor performance. Significance: Our findings are not in line with previous experiments in poststroke patients. However, long-term treatment with fluoxetine may additionally improve motor function by upregulating serotonergic receptors. Further studies investigating the influence of long-term treatment on cortical excitability and psychophysics may therefore provide deeper insight into a possible therapeutical efficiency of fluoxetine in poststroke patients.