title: Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors.
abstract: OBJECTIVE
  Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice.
  
  
  METHODS
  Female mice were injected with sertraline or saline throughout pregnancy. Offspring continued to receive injections on postnatal days 1-14, a time period in mice similar to the third trimester in human pregnancy. Adult offspring underwent behavioral testing, and serotonin receptor mRNA levels were quantified.
  
  
  RESULTS
  Compared to controls, SSRI exposed mice did not have a reduction in social interactions, spatial learning, or exploratory behavior. As adults, sertraline exposed mice had significantly increased mRNA levels of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex.
  
  
  CONCLUSIONS
  Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI exposure.
authors.affiliation: a Department of Pediatrics , Sanford Health , Sioux Falls , SD , USA.
authors.forename: Lauritz R
authors.initials: LR
authors.lastname: Meyer
authors.affiliation: b Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA , USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dexter
authors.affiliation: b Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA , USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lo
authors.affiliation: b Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA , USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kenkel
authors.affiliation: c Kindai University Faculty of Medicine , Higashiosaka, Osaka , Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Hirai
authors.affiliation: d Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA , USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
authors.affiliation: d Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA , USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Haskell
mesh_terms: D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012919:Social Behavior; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: Maternal depression; behavior; development; mice; selective serotonin reuptake inhibitors