A Developmental Neurotoxicity Evaluation of the Effects of Prenatal Exposure to Fluoxetine in Rats

Fluoxetine is a widely used serotonin reuptake inhibitor effectivein the treatment of depression. This experiment assessed thepotential developmental neurotoxicity of fluoxetine. Sprague-DawleyCD rats were treated once per day on Days 7–20 of gestationwith 0, 1, 5, or 12 mg/kg of fluoxetine (free base) dissolvedin distilled water. One control group received water by gavage;animals in this group were provided food and water ad libitum.The second control group (PF) also received water by gavage;animals in this group had their food and water restricted bypair-feeding and watering them to the 12 mg/kg fluoxetine group.Litters were culled to 12 after birth and offspring (male/femalepairs) were tested neurobehaviorally at three developmentalstages (preweaning, juvenile, and adult). At each stage, twopairs per litter received tests of locomotor activity, acousticstartle, and startle after administration of one of two pharmacologicalchallenges (one pair each receiving fluoxetine or apomorphine).Two pairs were also tested for spontaneous alternation, passiveavoidance, and complex learning in a water maze. At the highestdose, fluoxetine caused maternal weight loss during pregnancy,reduced litter sizes at birth, and increased neonatal mortality.No effects on long-term growth or survival were seen. Prenatalfluoxetine exposure produced no significant effects on locomotoractivity, spontaneous alternation, passive avoidance, or watermaze performance. A few scattered interactions involving treatmentgroup were obtained on startle, but no pattern of treatment-relatedchanges was evident. Regional wet and dry brain weights takenat each stage were not affected by prenatal fluoxetine exposure.The data suggest that fluoxetine is not developmentally neurotoxicin the rat.