Developmental and Behavioral Consequences of Prenatal Fluoxetine

Abstract

Background: Fluoxetine, a selective serotonin reuptake inhibitor, is the most commonly prescribed antidepressant drug for pregnant women. Studies regarding the teratogenic effect of fluoxetine on human and animal models are mainly concerned with structural malformation (congenital anomalies). Aim: Hence, the present study was planned to evaluate the postnatal behavioral effects of fluoxetine on albino rats. Methods: Three groups of female rats received either distilled water or doses of fluoxetine 8 and 12 mg/kg orally from the 6th to the 20th day of pregnancy. Weaning of the pups was done on the 21st day followed by a battery of behavioral tests to assess for any behavioral effect. The tests included negative geotaxis, open field exploration, rota-rod test, elevated plus maze and passive avoidance test. Results: In the present study there was no change in the gestational length of pregnancy, no premature birth or miscarriage during pregnancy. A high dose of in utero fluoxetine resulted in a decrease in birth weight of the offspring and also reduced weight gain during the preweaning period. No major congenital abnormalities were observed in the offspring exposed to fluoxetine. Prenatal fluoxetine exposure at high dose caused an initial transient delay in motor development and this poor motor activity was transient and not permanent. However, prenatal exposure to fluoxetine at a higher dose showed a favorable effect on learning and memory in water maze and passive avoidance tests. Conclusions: From the present study, it may be concluded that prenatal fluoxetine causes a transient delay in motor development but does not adversely affect the postnatal behavioral consequences.

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

“…Alterations in locomotion may be a potential confound in behavioral tests, and false-positives in anxiety-like behavior, for example, may be attributed to altered locomotion. Studies have shown that prenatal fluoxetine exposure increases activity and improves motor coordination in the rotorod test (Bairy et al, 2007). A similar finding was reported with prenatal bupropion exposure (Su et al, 2007).…”

“…Several animal studies examined these properties in the context of prenatal SSRI exposure with conflicting results. Impaired weight gain, low birth weight, or small litter size after prenatal SSRI exposure has been reported in several studies (da-Silva et al, 1999;Bairy et al, 2007;Pereira et al, 2007;Cagiano et al, 2008;Favaro et al, 2008;Forcelli and Heinrichs, 2008;Noorlander et al, 2008;Van den Hove et al, 2008;Bauer et al, 2010), whereas other studies observe no differences in weight gain or birth weight (Byrd and Markham, 1994;Stewart et al, 1998;Vartazarmian et al, 2005;Lisboa et al, 2007). Congenital malformations are reported in the clinical literature but have only been reported in the animal literature by extracting and exposing mouse embryos in vitro to 20 times the clinically observed serum concentration of sertraline for 48 hours (Shuey et al, 1992).…”

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

“…Bairy et al concluded that prenatal fluoxetine administered to rats caused weight loss and a delay in the transient motor development of fetuses, although it did not, however, compromise postnatal behavior, thus supporting the findings of Speiser et al 21,29 Most studies demonstrate that fluoxetine-treated rats bear low weight offspring. Vartazarmian et al, however, found no weight alterations in fetuses of fluoxetine-treated rats.…”

“…20 This study evaluated the possible macroscopic alterations i.e., weight of the fetuses, placentas and encephala and the microscopic alterations i.e., the quantification of frontal lobe nerve cells seen in the fetuses of rats intraperitoneally injected with 10mg/kg/day of fluoxetine and imipramine hydrochloride on the 9 th , 10 th and 11 th day of pregnancy. Fluoxetine was selected for being the antidepressant of choice for pregnant women while 13,21 imipramine was chosen for being a tricyclic antidepressant known to be potentially teratogenic. 22,23 The intraperitoneal route was chosen for being more secure, for providing a faster absorption by the rich blood supply of the large peritoneal area, for not presenting traumatic risks during administration and for constituting a routine laboratory procedure.…”

Early Pharmacotherapy Restores Neurogenesis and Cognitive Performance in the Ts65Dn Mouse Model for Down Syndrome

“…The current study shows that it is possible to increase cell proliferation in numerous regions of the postnatal brain in a mouse model for DS. We have used fluoxetine to stimulate neurogenesis, because it is an antidepressant widely used by adults and prescribed in children and adolescents (Boylan et al, 2007) and it has no patent aversive effects on somatic development (Bairy et al, 2007;Einarson et al, 2009). Treatment during the early postnatal period restored neurogenesis and led to the restoration of the total number of neurons in the dentate gyrus.…”