Effects of Prenatal and Lactational Vortioxetine Exposure on Emotional States, Motor Activities and Cognitive Performances of Offspring

Abstract

Objective: Pregnancy and breastfeeding are periods when hormonal fluctuations in women are intense and the risk of mood disorders is high. Uncured psychiatric disorders reduces the mother's quality of life on the one hand and harms the developing fetus on the other. The inability of mothers with psychiatric problems to provide the necessary care to their babies after birth and during the lactational period is another risk factor for the baby. For this reasons, the prescription of antidepressants to pregnant women has become increasingly common in recent years. On the other hand, studies indicate that exposure to antidepressants in the early stages of life causes some negative effects on the neurodevelopmental process of the fetus. Hence, it is of clinical importance to clarify the risks caused by the use of antidepressants during pregnancy. Therefore, it was aimed to investigate potential effects of prenatal and lactational exposure to vortioxetine, which is a relatively new antidepressant with a multimodal mechanism of action, on the emotional states, motor behaviors and cognitive performances of the offspring, in this study. Methods: Vortioxetine was administered orally to adult Sprague Dawley female rats at doses of 10 and 20 mg/kg/day before conception and continuing until the pups were weaned (P21). Behavioral experiments were performed with 90-day-old (P90) adult offspring. Motor activity, anxiety, depression and cognitive performance parameters of the rats were assessed using activity-meter, elevated plus-maze, modified forced swimming and passive avoidance tests, respectively. Results: Data from activity-meter tests revealed that prenatal and lactational exposure to vortioxetine (20 mg/kg) resulted in significant increases in horizontal, ambulatory, and stereotypic activity counts and walking distance values of the offspring, suggesting that vortioxetine exposure induced hyperactivity in these animals. In contrast, early-life vortioxetine exposure did not alter the number of vertical movements, indicative of exploratory behavior in rats. This finding, together with data showing that the offspring's preference for the open arm in elevated plus-maze tests was reduced, pointed out that these animals had increased anxiety levels. When the findings of the modified forced swimming tests were examined, it was detected that the duration of active swimming and climbing behaviors of rats increased and the immobility period shortened. These findings are thought to be related to an increase in the motor activity of the offspring rather than a decrease in the animals' depressive behavior. In the passive avoidance tests, it was observed that vortioxetine exposure did not cause any significant changes in the emotional learning and memory performances of the offspring. Conclusion: The findings obtained in this study showed that maternal exposure to vortioxetine, especially at high doses, may not be safe for the baby and suggested that this drug may not be superior to other antidepressants in terms of use at prenatal and lactational periods. On the other hand, comprehensive clinical studies are needed on children of mothers who used this drug before birth and during breastfeeding to gain a clearer understanding of the short - and long-term effects of early-life vortioxetine exposure on children.