title: Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats.
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.
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
authors.forename: Chase H
authors.initials: CH
authors.lastname: Bourke
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
authors.forename: Darin E
authors.initials: DE
authors.lastname: Olson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects*; D015283:Citalopram / Q000009:adverse effects*; D004702:Endocrine Glands / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram
keywords: ACTH; CRF; GN; Gene expression; HPA; Hypothalamic–pituitary–adrenal axis; Microarray; Neuropharmacology; PNDN; Prenatal antidepressant exposure; Prenatal stress; SAM; adrenocorticotropic hormone; corticotropin-releasing factor; gestational day N; hypothalamic–pituitary–adrenal; postnatal day N; significance analysis of microarray
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