Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring

• Published in: Developmental psychobiology Vol. 58; no. 4; pp. 427 - 438
• Main Authors: Boulle, Fabien, Pawluski, Jodi L., Homberg, Judith R., Machiels, Barbie, Kroeze, Yvet, Kumar, Neha, Steinbusch, Harry W. M., Kenis, Gunter, Van den Hove, Daniel L. A.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-05-2016; Wiley
• Subjects: Animals; Anxiety - chemically induced; Anxiety - etiology; BDNF; Behavior, Animal - drug effects; Behavior, Animal - physiology; Brain-Derived Neurotrophic Factor - metabolism; depression; Development Biology; Disease Models, Animal; Embryology and Organogenesis; Female; Fluoxetine - administration & dosage; Fluoxetine - adverse effects; Gene Expression; hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Life Sciences; Male; Neurobiology; Neurons and Cognition; neuroplasticity; Pregnancy; Prenatal Exposure Delayed Effects; prenatal stress; Psychology and behavior; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; sex differences; SSRI; Stress, Psychological - complications; TrkB; SSRI; TrkB; hippocampus; BDNF; prenatal stress; depression; sex differences; neuroplasticity; Neuroplasticity; SEX DIFFERENCES; Hippocampus
• ISSN: 0012-1630; 1098-2302
• DOI: 10.1002/dev.21385

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. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 427–438, 2016.