title: Chronic fluoxetine treatment changes S100B expression during postnatal rat brain development.
abstract: BACKGROUND
  Fluoxetine, a selective serotonin reuptake inhibitor, is approved for treatment of childhood depression. In rats, fluoxetine influences neuronal development, but it is unclear whether it also influences glia development. S100B is a glia-derived calcium-binding protein, which may influence the development of serotonergic fibers and, vice versa, serotonin may influence the expression of S100B.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether fluoxetine treatment influences the expression of S100B during postnatal development, and whether potential changes are regionally dependent upon the time frame of drug administration.
  
  
  METHODS
  S100B gene expression and S100B protein expression in three different brain regions (frontal cortex, hippocampus, and striatum) were studied by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. First, a short-term effect, 24 hours after a 14 day fluoxetine treatment (5 mg/kg/bw s.c.) of rats either from postnatal day (PD) 1 to 15, 21 to 35, or 50 to 64, was investigated. Then, the same treatment was used to analyze S100B gene and protein levels at PD 90 (long-term effect).
  
  
  RESULTS
  At PD 90, a significant increase of gene and protein expression was observed in all regions if rats were treated during PDs 21-35, whereas treatment during other periods had no long-term effects. A short-term effect 24 hours after fluoxetine treatment was found for almost all development stages and regions, demonstrated by a significant increase of S100B.
  
  
  CONCLUSIONS
  These results support recent research indicating a highly drug-sensitive period (i.e., periadolescence) of rat brain development. Therefore, further clinical studies should be performed to clarify whether such a sensitive period also exists in children.
authors.affiliation: 1 Department of Child and Adolescent Psychiatry, Georg-August-University of Göttingen , Göttingen, Germany .
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bock
authors.forename: Emre
authors.initials: E
authors.lastname: Koc
authors.forename: Hannah
authors.initials: H
authors.lastname: Alter
authors.forename: Veit
authors.initials: V
authors.lastname: Roessner
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Till
authors.initials: T
authors.lastname: Manzke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit / Q000096:biosynthesis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D005473:Fluoxetine; D064568:S100 Calcium Binding Protein beta Subunit; D017367:Selective Serotonin Reuptake Inhibitors; C579158:S100b protein, rat
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