Long-term effects of pre-gestational stress and perinatal venlafaxine treatment on neurobehavioral development of female offspring

Abstract

Preclinical studies suggest that stress-related disorders even prior gestation can cause long-term changes at the level of neurobehavioral adaptations. Therefore, it is critical to consider undergoing antidepressant therapy which could reverse the negative consequences in the offspring. Venlafaxine is widely used in clinical practice; however insufficient amount of well-controlled studies verified the safety of venlafaxine therapy during gestation and lactation. The aim of this work was to investigate the effects of perinatal venlafaxine therapy on selected neurobehavioral variables in mothers and their female offspring using a model of maternal adversity. Pre-gestational stressed and non-stressed Wistar rat dams were treated with either venlafaxine (10 mg/kg/day) or vehicle during pregnancy and lactation. We have shown that pre-gestational stress decreased the number of pups with a significant reduction in the number of males but not females. Furthermore, we found that offspring of stressed and treated mothers exhibited anxiogenic behavior in juvenile and adolescent age. However, during adulthood pre-gestational stress significantly increased anxiety-like behavior of female, with venlafaxine treatment normalizing the state to control levels. Additionally, we found that even maternal stress prior gestation can have long-term impact on adult number of hippocampal immature neurons of the female offspring. A number of questions related to the best treatment options for maternal depression still remains, however present data may provide greater insight into the possible outcomes associated with perinatal venlafaxine therapy.