title: Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.
abstract: OBJECTIVE
  Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we used a mouse model of focal cortical stroke to test 2 hypotheses. First, we investigated whether responsiveness to training decreases over time after stroke. Second, we tested whether fluoxetine, which can influence synaptic plasticity and stroke recovery, can prolong the period over which large training-related gains can be elicited after stroke.
  
  
  METHODS
  Mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent stroke induction in the caudal forelimb area. The mice were then retrained after a 1- or 7-day delay with and without fluoxetine.
  
  
  RESULTS
  Recovery of prehension after a caudal forelimb area stroke was complete if training was initiated 1 day after stroke but incomplete if it was delayed by 7 days. In contrast, if fluoxetine was administered at 24 hours after stroke, then complete recovery of prehension was observed even with the 7-day training delay. Fluoxetine seemed to mediate its beneficial effect by reducing inhibitory interneuron expression in intact premotor cortex rather than through effects on infarct volume or cell death.
  
  
  CONCLUSIONS
  There is a gradient of diminishing responsiveness to motor training over the first week after stroke. Fluoxetine can overcome this gradient and maintain maximal levels of responsiveness to training even 7 days after stroke.
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Kwan L
authors: KL
authors: Ng
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Ellen M
authors: EM
authors: Gibson
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Robert
authors: R
authors: Hubbard
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Juemin
authors: J
authors: Yang
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Brian
authors: B
authors: Caffo
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: Richard J
authors: RJ
authors: O'Brien
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.).
authors: John W
authors: JW
authors: Krakauer
authors: From the Departments of Neurology (K.L.N., E.M.G., R.H., J.W.K., S.R.Z.) and Neuroscience (J.W.K.), Johns Hopkins University, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.Y., B.C.); and Department of Neurology, Duke University, Durham, NC (R.J.O.). sz@jhmi.edu.
authors: Steven R
authors: SR
authors: Zeiler
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009044:Motor Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009048:Motor Skills / Q000187:drug effects; D009068:Movement / Q000187:drug effects; D000066530:Neurological Rehabilitation; D009473:Neuronal Plasticity / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020521:Stroke / Q000473:pathology / Q000503:physiopathology; D000071939:Stroke Rehabilitation; D061665:Time-to-Treatment
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: fluoxetine; motor cortex; neuronal plasticity; recovery; stroke; upper extremity