4.4 Article

Prenatal exposure to escitalopram and/or stress in rats

Journal

PSYCHOPHARMACOLOGY
Volume 228, Issue 2, Pages 231-241

Publisher

SPRINGER
DOI: 10.1007/s00213-013-3030-z

Keywords

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

Funding

  1. National Institutes of Health National Institute of Mental Health [P50 MH-77928]
  2. National Institute of Environmental Health Sciences [12870]
  3. National Center for Research Resources [012870]
  4. Howard Hughes Medical Institute [5600672]
  5. Emory Biomarker Service Center

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A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. 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. 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. 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.

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