Prenatal treatment with the antidepressant fluoxetine on maternal and neonatal behavior in sheep

Fluoxetine is commonly prescribed to treat depression during pregnancy. We aimed to evaluate the effects of prenatal fluoxetine exposure on maternal-offspring behavior in a non-depressed sheep model.

On day 119 ± 1 of a 151-day expected gestation, Hampshire ewes were randomly assigned to receive intravenous fluoxetine (10 mg/kg for the first 2 days and 5 mg/kg daily thereafter until parturition) or a control vehicle. Video was recorded of 8 fluoxetine-treated ewes and 10 control ewes for 2 h before and after parturition.

Fluoxetine did not alter dam behavior during the peripartum period, including time spent lying before the first birth, lying bout duration, probability of needing birth assistance, duration of birth assistance when provided, and time spent touching her lambs. However, in utero exposure impaired neonatal vigor as lambs spent less time standing and tended to spend less time nursing compared to unexposed lambs.

Neonatal behavioral impairments are consistent with those associated with fluoxetine exposure during human gestation. This effect appears to be independent of maternal behavior, which was unaffected by antidepressant use.

Lambs exposed to SSRI in utero spent less time standing and tended to spend less time nursing than control lambs, consistent with neonatal behavioral outcomes encountered in clinical practice. The reduced neonatal vigor was likely unrelated to maternal behavior, which was not altered by SSRI treatment. Non-depressed sheep models can help to elucidate the behavioral effects of antidepressant use during pregnancy to enhance health outcomes and patient care.