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Journal of the Society for Gynecologic Investigation
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Maternal Fluoxetine Infusion Does Not Alter Fetal Endocrine and Biophysical Circadian Rhythms in Pregnant Sheep

Janna L. Mornson, PhD

Department of Obstetrics and Gynecology, BC Research Institute for Children's & Women's Health; Faculty of Pharmaceutical Sciences, University of British Columhia, Vancouver, BC, Canada; Department of Obstetrics and Gynaecology and Discipline of Physiology, University of Adelaide, Adelaide, SA, Australia janna.momson{at}adelaide.edu.au

Dan W. Rurak, DPhil

Caly Chien, PhD

David J. Kennaway, PhD

Nancy Gruber, MSc

I. Caroline McMillen, DPhil

K. Wayne Riggs, PhD

Department of Obstetmcs and Gynecology, BC Research Institute for Children's & Women's Health; Faculty of Pharmaceutical Sciences, University of Bnrtish Columhia, Vancouver, BC, Canada; Department of Obstetrics and Gynaecology and Discipline of Physiology, University of Adelaide, Adelaide, SA, Australia

Objective: Depression during pregnancy is frequently treated with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (FX), commonly known as Prozac (Eli Lilly & Co, Indianapolis, IN). FX potentiates serotoninergic neurotransmission and serotonin has been implicated in the regulation of circadian rhythms. We have therefore investigated the effect of chronic administration of FX on maternal and fetal circadian rhythms in sheep.

Methods: Following an initial bolus dose of 70 mg FX, an 8-day continuous infusion of FX (n = 11, 98.5 µ/kg· d) was performed. Controls (n = 13) were treated with sterile water vehicle only. Maternal and fetal plasma melatonin and prolactin concentrations were determined every 3 hours for 24 hours and then every 6 hours for 24 hours beginning on the fourth day of infusion.

Results: FX treatment did not alter either the basal or circadian rhythms of either maternal or fetal plasma melatonin and prolactin concentrations. Fetal cardiovascular and behavioral state parameters were measured continuously. While the incidence of low-voltage (LV) electrocortical (ECOG) activity was significantly reduced in fetuses in the FX group, there was no effect of FX on the diurnal rhythms in fetal arterial pressure, heart rate, breathing movements, or behavioral state.

Conclusion: These results show that maternal FX treatment does not result in significant alterations in maternal and fetal hormonal and behavioral circadian rhythms.

Key Words: Fetal sheep • fluoxetine • melatonin • prolactin • fetal behavioral state

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 5, 356-364 (2005)
DOI: 10.1016/j.jsgi.2005.03.001
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