Abstract
Depression during pregnancy is frequently treated with the selective serotonin reuptake inhibitor, fluoxetine (FX). FX increases serotonergic neurotransmission and serotonin plays a role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have therefore investigated the effect of chronic administration of FX to the pregnant ewe on the maternal and fetal HPA axes. Nineteen late-gestation sheep were surgically prepared for chronic study of the fetus. FX (n = 7, 98.5 μg/kg/d) or sterile water (control, n = 8) was administered to the ewe for 8 d by constant rate i.v. infusion with an initial FX bolus dose of 70 mg. Maternal and fetal plasma ACTH and cortisol concentrations were determined at 0700 h each day. Maternal plasma ACTH concentrations fell on infusion d 2, but no changes were observed in maternal plasma cortisol concentrations. Fetal plasma ACTH concentrations increased on infusion d 7, and fetal plasma cortisol concentrations increased on infusion d 6, 7, and 8 in the FX group. In addition, the regression coefficient for the relationship between fetal ACTH and cortisol levels was significantly greater in the FX group compared with the control group. Thus, maternal FX treatment increased fetal plasma cortisol concentration. These results are of particular interest in the context that exposure of the fetus to excess glucocorticoids at critical windows during development has been shown to increase the risk of poor health outcomes in later life.
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Abbreviations
- SSRI:
-
selective serotonin reuptake inhibitor
- FX:
-
fluoxetine
- HPA:
-
hypothalamic-pituitary-adrenal
- ACTH:
-
adrenocorticotrophin
- NFX:
-
norfluoxetine
- CRH:
-
corticotrophin-releasing hormone
- AVP:
-
arginine vasopressin
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Acknowledgements
The authors thank Anne Jurisevic for her expert research assistance.
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Supported by a grant from the Canadian Institutes of Health Research (CIHR). D.W.R. is the recipient of an investigatorship award from the British Columbia Research Institute for Children's & Women's Health. J.L.M. is the recipient of a CIHR Studentship. C.C. is the recipient of a PMAC/HRF-CIHR studentship. Novopharm Ltd., Toronto, ON, Canada, generously donated the fluoxetine hydrochloride used in these studies.
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Morrison, J., Riggs, K., Chien, C. et al. Chronic Maternal Fluoxetine Infusion in Pregnant Sheep: Effects on the Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes. Pediatr Res 56, 40–46 (2004). https://doi.org/10.1203/01.PDR.0000128981.38670.28
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DOI: https://doi.org/10.1203/01.PDR.0000128981.38670.28
