title: Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats.
abstract: BACKGROUND
  Epilepsy is a central disorder associated with neuronal damage and brain hypometabolism. It has been reported that antidepressant drugs show anticonvulsant and neuroprotective effects in different animal models of seizures and epilepsy.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the eventual short-term brain impairment induced by a single low convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP) and the eventual neuroprotective effects exerted by fluoxetine, a prototypical selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI).
  
  
  METHODS
  In vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and several histological assessments were carried out in adult male rats after i.p. administration of 3 mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage. We also evaluated the effects of a short-term fluoxetine treatment (10 mg/kg, i.p. for 7 days) in this seizure model.
  
  
  RESULTS
  [18F]FDG PET analysis revealed no changes in the regional brain metabolism on day 3 after 4-AP injection. The histological assessments revealed signs of damage in the hippocampus, a brain area usually affected by seizures. Thus, reactive gliosis and a significant increase in the expression of caspase-9 were found in the aforementioned brain area. By contrast, we observed no signs of neurodegeneration or neuronal death. Regarding the effects of fluoxetine, this SSRI showed beneficial neurologic effects, since it significantly increased the seizure latency time and reduced the abovementioned 4-AP-induced hippocampal damage markers.
  
  
  CONCLUSIONS
  Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective agents against convulsant-induced hippocampal damage.
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid. Spain.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Shiha
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid. Spain.
authors.forename: Rubén Fernández
authors.initials: RF
authors.lastname: de la Rosa
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid. Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid. Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pozo
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid. Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: García-García
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity*; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005473:Fluoxetine / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D015761:4-Aminopyridine; D053453:Caspase 9; D003292:Convulsants; D005452:Fluoresceins; D019788:Fluorodeoxyglucose F18; D005473:Fluoxetine; D005904:Glial Fibrillary Acidic Protein; D010751:Phosphopyruvate Hydratase; D017367:Selective Serotonin Reuptake Inhibitors; C534582:fluoro-jade C
keywords: 4-aminopyridine; astrogliosis; brain metabolism; fluoxetine; hippocampus; positron emission tomography; seizure; selective
  serotonin reuptake inhibitor