![]() Stroke is the second cause of death worldwide and the leading cause of death in upper-middle income countries about 6.7 million people died from stroke in 2013 in the US ( Mozaffarian et al., 2016). ![]() This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. 7Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Harvard University, Boston, MA, United States.6Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Harvard University, Boston, MA, United States.5Stroke Biological Recovery Laboratory, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Harvard University, Boston, MA, United States.4Highland Instruments, Cambridge, MA, United States.3Department of Severe Patients, Hospital Israelita Albert Einstein, São Paulo, Brazil.2Department of Neuroscience and Behavior, Psychology Institute, University of São Paulo, São Paulo, Brazil.1Laboratory of Neuromodulation and Center for Clinical Research Learning, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Harvard University, Boston, MA, United States.Camargo 7, Randie Black-Schaffer 6 and Felipe Fregni 1 * ![]() de Toledo Piza 1,3, Laura Dipietro 4, Qing M. Saleh Velez 1, Fernanda Lopes 1, Polyana V. ![]()
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