Maternal fluoxetine infusion does not alter fetal endocrine and biophysical circadian rhythms in pregnant sheep.
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 microg/kg x 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.


CONCLUSIONS
These results show that maternal FX treatment does not result in significant alterations in maternal and fetal hormonal and behavioral circadian rhythms.
Department of Obstetrics and Gynecology, BC Research Institute for Children's & Women's Health, University of British Columbia, Vancouver, BC, Canada. janna.morrison@adelaide.edu.au <janna.morrison@adelaide.edu.au>
Janna L
JL
Morrison
Dan W
DW
Rurak
Caly
C
Chien
David J
DJ
Kennaway
Nancy
N
Gruber
I Caroline
IC
McMillen
K Wayne
KW
Riggs
D000818:Animals; D001794:Blood Pressure; D002940:Circadian Rhythm / Q000187:drug effects*; D004562:Electrocardiography; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D008550:Melatonin / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011388:Prolactin / Q000097:blood; D012119:Respiration; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep
D005473:Fluoxetine; D008550:Melatonin; D011388:Prolactin; D017367:Selective Serotonin Reuptake Inhibitors