title: Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.
abstract: Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.
authors.affiliation: Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ine
authors.initials: I
authors.lastname: Rayen
authors.forename: Daniël L
authors.initials: DL
authors.lastname: van den Hove
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
authors.forename: Harry W
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Pawluski
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy; D000089622:Doublecortin Domain Proteins; D005260:Female; D005333:Fetus / Q000502:physiology*; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013312:Stress, Physiological / Q000187:drug effects; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D000089622:Doublecortin Domain Proteins; D005473:Fluoxetine; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017367:Selective Serotonin Reuptake Inhibitors