title: Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring.
abstract: BACKGROUND
  Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the unborn child has not yet been established. Fluoxetine, a selective serotonin reuptake inhibitor, crosses the placenta, leading to increased extracellular serotonin levels and potentially neurodevelopmental changes in the fetus.
  
  
  OBJECTIVE
  The purpose of this study was to elucidate the long-term consequences of prenatal fluoxetine in rats.
  
  
  METHODS
  Pregnant rats were injected daily with 12 mg/kg fluoxetine or vehicle from gestational day 11 until birth, and the behavior of the offspring was monitored.
  
  
  RESULTS
  Plasma fluoxetine transfer from mother to pup was 83%, and high levels of fluoxetine (13.0 μg/g) were detected in the pup brain 5 h after the last injection. Fluoxetine-treated dams gave birth to litters 15% smaller than usual and to pups of reduced weight (until postnatal day 7). Furthermore, prenatal fluoxetine exposure significantly increased anxiety in the novelty-suppressed feeding test, the footshock-induced conditioned place aversion test, and the elevated plus maze test (following footshock pre-exposure) during adulthood, and also significantly decreased components of social play behavior at 4 weeks of age, and a strong tendency for increased self-grooming and making less contact in adults. Behavioral despair, anhedonia, and sexual behavior were not different between treatment groups. Finally, the hypothermic response to the 5-HT(1A) agonist flesinoxan was observed at a lower dose in prenatally fluoxetine-exposed rats than in controls.
  
  
  CONCLUSIONS
  Prenatal fluoxetine exposure in rats leads to detrimental behavioral outcomes in later life, which may partly be due to altered 5-HT(1A) receptor signaling.
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21 (route 126), 6525, EZ, Nijmegen, The Netherlands.
authors.forename: Jocelien D A
authors.initials: JD
authors.lastname: Olivier
authors.forename: A
authors.initials: A
authors.lastname: Vallès
authors.forename: Floor
authors.initials: F
authors.lastname: van Heesch
authors.forename: Anthonieke
authors.initials: A
authors.lastname: Afrasiab-Middelman
authors.forename: Janneke J P M
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Marloes
authors.initials: M
authors.lastname: Jonkers
authors.forename: Elke Joan
authors.initials: EJ
authors.lastname: Peeters
authors.forename: Gerdien A H
authors.initials: GA
authors.lastname: Korte-Bouws
authors.forename: Jos P
authors.initials: JP
authors.lastname: Dederen
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Martens
authors.forename: Dirk
authors.initials: D
authors.lastname: Schubert
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008431:Maternal-Fetal Exchange; D018782:Maze Learning / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012919:Social Behavior; D013550:Swimming
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors