Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

• Type of Material: Article
• Authors: Chase H. Bourke, Emory University; Catherine F. Capello, Emory University; Swati M. Rogers, Emory University; Megan L. Yu, Emory University; Katherine A. Boss-Williams, Emory University; Jay M Weiss, Emory University; Zachary N. Stowe, University of Arkansas; Michael J Owens, Emory University
• Language: English
• Date: 2013-07
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013, Springer-Verlag Berlin Heidelberg
• Final Published Version (URL): http://link.springer.com/article/10.1007%2Fs00213-013-3030-z
• Title of Journal or Parent Work: Psychopharmacology
• ISSN: 0033-3158
• Volume: 228
• Issue: 2
• Start Page: 231
• End Page: 241
• Grant/Funding Information: This work was supported by the National Institutes of Health National Institute of Mental Health [Grant P50 MH-77928] (ZNS and MJO) and 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.; ZNS has received research support from NIH, GSK, Pfizer and Wyeth; MJO has research grants from NIH, Eli Lilly, Lundbeck A/S, Cyberonics, Ortho-McNeil Janssen, AstraZeneca, Dainippon Sumitomo Pharma, Sunovion, and SK Life Sciences
• Keywords: animal models; maternal care; stress; pharmacokinetics; hypothalamic-pituitary-adrenal axis; pregnancy; selective serotonin reuptake inhibitor; developmental pharmacology
• Research Categories: Biology, Neuroscience; Health Sciences, Pharmacology

Abstract

Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition.