Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study

Abstract

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p < 0.01): G1 weighed more than G2 and G3. Otherwise, G2 exhibited the highest encephalon weight, statistically differing from G3 (control) and fluoxetine-treated G1 (p < 0.01). However, G1 did not statistically (p > 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p < 0.01). CONCLUSION: The use of antidepressants in rats caused an increase in fetal weight and a decrease in the number of fetal frontal lobe neurons, thus suggesting that the use of antidepressants by pregnant women can induce depression in fetuses due to alterations in their neural development.

Forced swim test behavior in postpartum rats

“…Additionally, studies in women suggest that antidepressant doses need to be increased to maintain euthymia during the second half of pregnancy (Hostetter et al, 2000; Sit et al, 2008), due to increased drug metabolism (Sit et al, 2008). Similar to the present findings, there are also previous reports of peri- and postnatal complications from antidepressant drug treatment during late pregnancy in rodents (Swerts et al, 2009; Van den Hove et al, 2008). However, in humans the primary adverse outcome of SSRI exposure during pregnancy appears to be preterm birth, which may also result from untreated depression (Bigos et al, 2009; Wisner et al, 2009).…”

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

“…Changes in birth weight or growth attributed to prenatal NRI exposure have been reported in the clinical literature. Animal studies show conflicting results; some report no changes in pup weight or litter size (Rodríguez Echandía and Broitman, 1983;De Ceballos et al, 1985b;Harmon et al, 1986;Stewart et al, 1998), an increase in fetal and neonatal weights (Cuomo et al, 1984;Swerts et al, 2010), or reduced birth weight in pups and reduced …”

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

“…It should also be noted that most preclinical research with regards to the effects of perinatal antidepressant medication exposure on neurobehavioral outcomes has investigated the effects of these antidepressant medications on offspring of healthy mothers [13,38,39,40,43]. However, because the primary action of antidepressant medications is to alleviate depressive symptoms, more preclinical research is needed on the impact of SSRIs on development in offspring subject to maternal adversity.…”

“…Research on the effect of SSRIs on brain development in rats has shown that fluoxetine treatment during gestation days (GD) 9–11 has no effect on fetal encephalic weight or the number of neurons in the frontal lobe at GD21 [43]. In contrast, treatment with imipramine, a tricyclic antidepressant, at the same time period during gestation, increases fetal brain weight and decreases neuron number in the frontal lobe of the fetal rat encephala at GD21 [43].…”

“…In contrast, treatment with imipramine, a tricyclic antidepressant, at the same time period during gestation, increases fetal brain weight and decreases neuron number in the frontal lobe of the fetal rat encephala at GD21 [43]. Thus, it appears that gross brain development is differentially affected by SSRI and tricyclic antidepressant medications.…”