title: Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity.
abstract: BACKGROUND
  During pregnancy and postpartum period, 20 % of women are affected by depression, which is a growing health concern. Selective serotonin reuptake inhibitor (SSRI) medications are popular treatments for maternal depression; however, the effect of maternal depression and perinatal SSRI exposure on offspring's neural development needs further investigation.
  
  
  OBJECTIVE
  This study aims to determine the role of developmental fluoxetine exposure on hippocampal plasticity in the adult offspring.
  
  
  METHODS
  Sprague-Dawley rat offspring were exposed to fluoxetine beginning on postnatal day 1. Offspring were also exposed to prenatal maternal stress. Four groups of male and female offspring were used: (1) prenatal stress + fluoxetine, (2) prenatal stress + vehicle, (3) fluoxetine alone, and (4) vehicle alone. Hippocampi were analyzed for levels of cell proliferation, immature neurons, and new cell survival (3 weeks after 5-bromo-2-deoxyuridine injection) in the granule cell layer, as well as synaptophysin density in the CA3 region and granule cell layer. TPH staining was assessed in the dorsal raphe nucleus.
  
  
  RESULTS
  Developmental fluoxetine exposure to prenatally stressed offspring reversed the effect of prenatal stress or fluoxetine exposure alone on the number of immature neurons. Prenatal stress alone, regardless of developmental exposure to fluoxetine, markedly decreased hippocampal cell proliferation and tended to decrease new cell survival. Furthermore, in adult female offspring, developmental fluoxetine exposure greatly increased new cell survival and significantly decreased synaptophysin density in the granule cell layer.
  
  
  CONCLUSIONS
  There are long-term effects of developmental SSRI exposure on hippocampal plasticity that is differentially affected by expose to maternal adversity and offspring sex.
authors.affiliation: School for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
authors.forename: Ine
authors.initials: I
authors.lastname: Rayen
authors.forename: Mary
authors.initials: M
authors.lastname: Gemmel
authors.forename: Grace
authors.initials: G
authors.lastname: Pauley
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Pawluski
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology*; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors