Effect of prenatal administration of venlafaxine on postnatal development of rat offspring

Abstract

About 3% of pregnant women are treated with antidepressant drugs during gestation. After delivery the number of treated women increases to 5 to 7%. Most prescribed antidepressants in pregnancy are selective serotonin re-uptake inhibitors and/or serotonin and noradrenaline re-uptake inhibitors, such as fluoxetine, paroxetine, sertraline, citalopram and venlafaxine (VENF). Despite the fact that VENF has been assigned to pregnancy category C by the FDA, experimental studies with this drug are rare. The aim of this pilot study was to investigate the effect of prenatal administration of VENF on early postnatal development of rat offspring and selected biochemical variables at weaning of pups. Pregnant female Wistar rats were treated with VENF from day 15 to 20 of gestation at the doses of 7.5, 37.5 and 70 mg/kg. Females were allowed to spontaneously deliver their pups. After delivery the pups were inspected for viability, gross malformation and they were weighed on day 0, 4 and 21 post partum. On day 21 post partum, the pups were killed, brains were removed from the skulls and blood samples were collected for biochemical assay (proteins, glucose-GOD, glucose-HEX, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and total antioxidant status). The study showed that prenatal VENF administration resulted in a mild maternal intoxication manifested by decreased body weight gain of pregnant females. There was no effect of the drug tested on the body and brain weights of offspring. No obvious morphological alterations were observed in the delivered pups. Similarly, there were no changes in the selected biochemical variables determined.

Keywords: fetus; noradrenaline re-uptake inhibitors; postnatal development; pregnancy; pups; rat; selective serotonin re-uptake inhibitors and/or serotonin; venlafaxine.

Figure 1

Effect of prenatal VENF on body weight of pregnant females. G – gestation, V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg; p<0.01 – statistically significant difference, repeated measures ANOVA (effect of time).

Figure 2

Effect of prenatal VENF on body weight gains of pregnant females. G – gestation, V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.

Figure 3

Effect of prenatal VENF on body weight of pups on day 0 post partum. V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.

Figure 4

Effect of prenatal VENF on body weight of pups on day 4 post partum. V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.

Figure 5

Effect of prenatal VENF on body weight of pups on day 21 post partum. V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.

Figure 6

Effect of prenatal VENF on the number of pups on day 0 post partum. V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.

Figure 7

Effect of prenatal VENF on brain weight of pups on day 21 post partum. V1 – VENF at dose 7.5 mg/kg, V2 – VENF at dose 37.5 mg/kg, V3 – VENF at dose 70 mg/kg.