title: Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring.
abstract: Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults.
  
  
  METHODS
  C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring.
  
  
  RESULTS
  Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive abilities, memory, sensorimotor information processing, or risk assessment behaviors. These results demonstrate that maternal exposure to stress and Flx have a number of sustained effects on the male offspring.
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Kiryanova
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Meunier
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: H A
authors.initials: HA
authors.lastname: Vecchiarelli
authors.affiliation: Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: M N
authors.initials: MN
authors.lastname: Hill
authors.affiliation: Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. Electronic address: rdyck@ucalgary.ca.
authors.forename: R H
authors.initials: RH
authors.lastname: Dyck
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000633:toxicity*; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D013315:Stress, Psychological
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: BDNF; SSRI; aggression; anxiety; behavior; prenatal stress