title: Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring.
abstract: With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior.
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.|Center for Psychiatry and Neuroscience, INSERM U894, University Pierre and Marie Curie, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Boulle
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.|University of Liege, GIGA-Neurosciences, 1 avenue de l'Hôpital (Bat. B36), B-4000 Liège, Belgium.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Pawluski
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Radboud University Medical Centre, Department of Cognitive Neuroscience, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Barbie
authors.initials: B
authors.lastname: Machiels
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Radboud University Medical Centre, Department of Cognitive Neuroscience, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Yvet
authors.initials: Y
authors.lastname: Kroeze
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Neha
authors.initials: N
authors.lastname: Kumar
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Maastricht University, European Graduate School of Neuroscience (EURON), Universiteitssingel 50, P.O. box 616, 6200 MD, Maastricht, The Netherlands.|Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany.
authors.forename: Daniel L A
authors.initials: DL
authors.lastname: Van den Hove
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000209:etiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors
keywords: BDNF; SSRI; TrkB; depression; hippocampus; neuroplasticity; prenatal stress; sex differences