Psychopharmacology

, Volume 228, Issue 2, pp 231–241 | Cite as

Prenatal exposure to escitalopram and/or stress in rats

A prenatal stress model of maternal depression and its treatment
  • Chase H. Bourke
  • Catherine F. Capello
  • Swati M. Rogers
  • Megan L. Yu
  • Katherine A. Boss-Williams
  • Jay M. Weiss
  • Zachary N. Stowe
  • Michael J. Owens
Original Investigation
First Online:
Received:
Accepted:

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 after 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.

Keywords

Animal models Developmental pharmacology Hypothalamic–pituitary–adrenal axis Maternal care Pharmacokinetics Pregnancy Selective serotonin reuptake inhibitor Stress 

Abbreviations

CMS

Chronic unpredictable mild stress

CRF

Corticotropin-releasing factor

GN

Gestational day N

PNDN

Postnatal day N

SSRI

Selective serotonin reuptake inhibitor

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Notes

Acknowledgements

We thank Dr. James Ritchie and Bailey Glover from the Department of Pathology and Laboratory Medicine at Emory University for running the serum escitalopram assay. We also thank Dr. K.V. Thrivikraman for help with the jugular catheterization surgery. Escitalopram oxalate was a generously provided by Lundbeck Research USA (Paramus NJ). All experiments comply with the current laws of the United States of America. 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.

Conflicts of interest

CHB, CFC, SMR, MLY, KAB, and JMW have no conflicts to disclose. 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. 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 to Takeda and RJ Reynolds. He receives consulting fees from H. Lundbeck A/S that are greater than $5,000 annually. These financial interests have been reviewed and a financial management plan is in place. He has a patent entitled: "Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters" (US 7,148,027 B2).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Chase H. Bourke
    • 1
  • Catherine F. Capello
    • 1
  • Swati M. Rogers
    • 1
  • Megan L. Yu
    • 1
  • Katherine A. Boss-Williams
    • 1
  • Jay M. Weiss
    • 1
  • Zachary N. Stowe
    • 2
  • Michael J. Owens
    • 1
  1. 1.Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral SciencesEmory UniversityAtlantaUSA
  2. 2.Department of Psychiatry, Pediatrics and Obstetrics and GynecologyUniversity of Arkansas for Medical SciencesLittle RockUSA

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