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Author Notes:

Corresponding Author: Michael J. Owens, Ph.D., Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, 101 Woodruff Circle, Suite 4000, Emory University, Atlanta, GA 30322, Voice: (404) 727-4059, Fax: (404) 727-3233, mowens@emory.edu

Escitalopram oxalate was generously provided by Lundbeck Research USA (Paramus, NJ).

We would like to thank Alicia Smith, Ph.D. for her advice during analysis of the microarray data and Catherine Capello and Faketa Zeljenovik for their assistance in breeding, treating and raising the animals.

ZNS has received research support from NIH, GSK, Pfizer and Wyeth, has served on speakers or advisory boards for Pfizer, Eli Lilly, Wyeth, BMS, and GSK, and has received honoraria from Eli Lilly, GSK, Pfizer, and Wyeth.

GNN receives grant funding from NIMH, AHA, NARSAD, GSK, and Emory University.

MJO has research grants from NIH, Eli Lilly, Lundbeck A/S, Cyberonics, Ortho-McNeil Janssen, AstraZeneca, Dainippon Sumitomo Pharma, Sunovion, and SK Life Sciences. He is a consultant for Takeda and RJ Reynolds. He receives consulting payments from H. Lundbeck A/S >$5,000 annually. He has a patent entitled: “Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters” (US 7,148,027 B2).

No other conflicts of interest to disclose.

Subjects:

Research Funding:

This work was supported by the National Institutes of Health National Institute of Mental Health [Grant 77928] (ZNS and MJO), the National Institute of Environmental Health Sciences [Grant 12870] (CHB), the National Center for Research Resources [Grant 012870] (CHB), the Howard Hughes Medical Institute [Grant 5600672] (CHB), and in part by the Emory Biomarker Service Center.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Toxicology
  • Neurosciences & Neurology
  • Gene expression
  • Hypothalamic-pituitary-adrenal axis
  • Microarray
  • Neuropharmacology
  • Prenatal antidepressant exposure
  • Prenatal stress
  • SEROTONIN-REUPTAKE INHIBITORS
  • ANTIDEPRESSANT EXPOSURE
  • PULMONARY-HYPERTENSION
  • MATERNAL DEPRESSION
  • IN-UTERO
  • WOMEN
  • METHYLATION
  • PROGENY
  • NEURONS
  • SYSTEM

Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats

Tools:

Journal Title:

Neurotoxicology and Teratology

Volume:

Volume 39

Publisher:

, Pages 100-109

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10-20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication.

Copyright information:

© 2013 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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