Perinatal exposure to venlafaxine leads to lower anxiety and depression-like behavior in the adult rat offspring

Depression during pregnancy and in the post-partum period is a growing health issue. Venlafaxine, a representative of serotonin and noradrenaline reuptake inhibitors, is used to treat a wide spectrum of mood disorders. However, the limited number of prenatal and perinatal studies raises the question about the long-term consequences of venlafaxine therapy. The aim of this study was to investigate the effect of venlafaxine exposure during pregnancy and lactation on anxiety-like and depression-like behaviors, as well as adrenocortical hormone concentrations in the adult rat offspring. For this purpose, rat dams were treated orally with venlafaxine from day 15 of gestation to postnatal day 20 at doses of 7.5, 37.5, and 75mg/kg. Administration of venlafaxine during gestation and lactation affected anxiety-like and depression-like behaviors in adult rat offspring of both sexes. The animals exposed through their mothers to venlafaxine, particularly at the lowest and middle doses, were less anxious and less depressive in several relevant behavioral tests, which can be considered a deviation from the normal state. At clinically relevant doses, venlafaxine did not alter circulating level of corticosterone and aldosterone in the adult offspring. In general, the consequences of venlafaxine were dose dependent and more apparent in females. Together, these results suggest that prenatal and early postnatal exposure to venlafaxine may interfere with functional development of the brain, though not necessarily in a negative way.