Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring

V Kiryanova; S J Meunier; H A Vecchiarelli; M N Hill; R H Dyck

doi:10.1016/j.neuroscience.2016.01.064

Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring

Neuroscience. 2016 Apr 21:320:281-96. doi: 10.1016/j.neuroscience.2016.01.064. Epub 2016 Feb 9.

Authors

V Kiryanova¹, S J Meunier¹, H A Vecchiarelli², M N Hill³, R H Dyck⁴

Affiliations

¹ Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
² Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
³ Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
⁴ 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.

PMID: 26872999
DOI: 10.1016/j.neuroscience.2016.01.064

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.

Keywords: BDNF; SSRI; aggression; anxiety; behavior; prenatal stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aggression / drug effects
Animals
Behavior, Animal* / drug effects
Brain / drug effects*
Disease Models, Animal
Female
Fluoxetine / toxicity*
Male
Maternal Behavior / drug effects
Mice
Mice, Inbred C57BL
Pregnancy
Prenatal Exposure Delayed Effects*
Selective Serotonin Reuptake Inhibitors / toxicity*
Stress, Psychological*

Substances

Serotonin Uptake Inhibitors
Fluoxetine

Grants and funding

Canadian Institutes of Health Research/Canada