Fetal behavioural state changes following maternal fluoxetine infusion in sheep

Clinical depression is diagnosed in 5-15% of women during pregnancy, increa sing the risk of negative outcomes. Fluoxetine (FX), a selective serotonin reuptake inhibitor, is prescribed during pregnancy. In adults, FX alters sl eep patterns with single doses decreasing total sleep time and rapid eye mo vement sleep. The effects of FX on sleep in the fetus are unknown. However, 5-hydroxytryptophan, the precursor of serotonin, has been reported to prol ong high-voltage (HV) electrocortical (ECoG) activity and increase the inci dence of fetal breathing movements (FBM) in the sheep fetus. We hypothesize that FX exposure will decrease the incidence of LV ECoG in the fetus. Twen ty-one pregnant sheep were surgically prepared for chronic study of blood g ases, ECoG activity, eye movements and FBM. After 3 days of recovery, ewes received a 70-mg bolus i.v. infusion of FX or sterile water followed by con tinuous infusion at a rate of 0.036 mg/min for 8 days. The incidence of low -voltage (LV) ECoG decreased from 54 +/-4% on the preinfusion day to 45 +/- 5% on infusion day I in the FX group and remained decreased throughout the infusion period. In addition, the incidence of both eye movements and FBM w as decreased on infusion day I compared to preinfusion day in the FX group. HV ECoG increased from 39 +/-3% on preinfusion day to 68 +/- 14% on FX inf usion day I and remained elevated throughout the infusion period. These dat a show that maternal FX administration alters fetal behavioural state. (C) 2001 Elsevier Science B.V. All rights reserved.