Perinatal fluoxetine exposure does not impair cognition in offspring

Abstract

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (FLX) are widely prescribed to treat depression during pregnancy, however their lasting effects on both maternal and offspring behavior remains uncertain. Long-term outcomes on cognitive performance in the offspring are mixed, and in addition the role of maternal care is understudied. In humans it is impossible to study the effect of SSRIs without the underlying maternal illness, therefore, our aim was to investigate the long-term effects of perinatal FLX exposure on cognitive performance of dams and their offspring in Wistar rats. Because serotonin levels can alter maternal care, this behavior was observed as well. Female rats were daily treated with either FLX or vehicle (VEH) throughout pregnancy and lactation. Dams were tested for spatial memory before pregnancy and six weeks after the pups were weaned. Male and female offspring were tested for spatial working memory, short-term and long-term spatial memory, and social recognition. We found that FLX-treated dams showed a higher frequency on the nest. Unfortunately, both mothers and offspring were not able to discriminate novel object location in short- and long-term memory test, therefore no conclusions could be drawn for this specific spatial memory test. Regarding other cognitive outcomes in the offspring, perinatal FLX did not influence spatial working memory and social recognition. Sex-specific effects were observed in which females, regardless of treatment, showed a higher cognitive flexibility but reduced social recognition compared to males. Our findings demonstrate that SSRIs use during pregnancy and lactation influences maternal care but has little impact on cognitive function of offspring.