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

• Type of Material: Article
• Authors: Chase H. Bourke, Emory University; Zachary Stowe, Emory University; Gretchen Neigh, Emory University; Darin Olson, Emory University; Michael Owens, Emory University
• Language: English
• Date: 2013-09-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ntt.2013.07.008
• Title of Journal or Parent Work: Neurotoxicology and Teratology
• ISSN: 0892-0362
• Volume: 39
• Start Page: 100
• End Page: 109
• Grant/Funding Information: 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: MATERNAL DEPRESSION; Life Sciences & Biomedicine; Toxicology; NEURONS; SEROTONIN-REUPTAKE INHIBITORS; Prenatal stress; PROGENY; Microarray; Neurosciences & Neurology; SYSTEM; IN-UTERO; Neurosciences; Prenatal antidepressant exposure; METHYLATION; Neuropharmacology; Gene expression; Science & Technology; WOMEN; ANTIDEPRESSANT EXPOSURE; PULMONARY-HYPERTENSION; Hypothalamic-pituitary-adrenal axis
• Research Categories: Biology, Neuroscience; Health Sciences, Toxicology

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.