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 plac… Show more
“…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).…”
This study was undertaken to determine whether depression-like behavior can be observed in gonadally intact females that have experienced normal pregnancy. When tested on the forced swim test (FST) on postpartum days 1-7, previously pregnant rats spent slightly more time immobile, significantly less time swimming and diving, and defecated more than virgin controls. Subchronic treatment with nomifensine (DA reuptake inhibitor, 2.5 mg/kg) but not sertraline (serotonin reuptake inhibitor, 10 mg/kg) or desipramine (norepinephrine reuptake inhibitor, 10 mg/kg) significantly decreased immobility on postpartum day 2. In rats pre-exposed to the FST in mid-pregnancy, neither subchronic nor chronic treatment with desipramine or sertraline decreased immobility on postpartum day 2; in contrast, chronic desipramine significantly decreased immobility in virgin controls. These results indicate that postpartum female rats, compared to virgin controls, show a reduction in some "active coping behaviors" but no significant increase in immobility when tested during the early postpartum period, unlike ovariectomized females that have undergone hormone-simulated pregnancy (HSP). Additionally, immobility that is increased by FST pre-exposure is not readily prevented by treatment with standard antidepressant medications in postpartum females. Depressionlike behaviors previously observed in females that have undergone HSP may result from the more dramatic changes in estradiol, prolactin or corticosterone that occur during the early "postpartum" period, compared to the more subtle changes in these hormones that occur in actual postpartum females.Keywords postpartum depression; females; antidepressants; forced swim test; gestational stress; estradiol; prolactin; corticosterone; pregnancy; nominfensine; sertraline; desipramine Previous studies suggest that hormonal changes that women undergo around the time of childbirth may trigger postpartum mood disorders O'Hara, 2009;Parry et al., 2003). We and others have shown previously that ovariectomized female rats that have undergone hormone-simulated pregnancy (HSP) show depression-like behaviors during the "postpartum" period, suggesting that HSP followed by hormone withdrawal may be a useful animal model of postpartum depression (Galea et al., 2001;Green et al., 2009;Navarre et al., 2010;Stoffel and Craft, 2004). In these studies, the abrupt hormone withdrawal at the end of the HSP (modeling parturition) is considered to be the stressor; rats that have undergone HSP and are tested only once during the "postpartum" period on the forced swim test (FST) or
“…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).…”
This study was undertaken to determine whether depression-like behavior can be observed in gonadally intact females that have experienced normal pregnancy. When tested on the forced swim test (FST) on postpartum days 1-7, previously pregnant rats spent slightly more time immobile, significantly less time swimming and diving, and defecated more than virgin controls. Subchronic treatment with nomifensine (DA reuptake inhibitor, 2.5 mg/kg) but not sertraline (serotonin reuptake inhibitor, 10 mg/kg) or desipramine (norepinephrine reuptake inhibitor, 10 mg/kg) significantly decreased immobility on postpartum day 2. In rats pre-exposed to the FST in mid-pregnancy, neither subchronic nor chronic treatment with desipramine or sertraline decreased immobility on postpartum day 2; in contrast, chronic desipramine significantly decreased immobility in virgin controls. These results indicate that postpartum female rats, compared to virgin controls, show a reduction in some "active coping behaviors" but no significant increase in immobility when tested during the early postpartum period, unlike ovariectomized females that have undergone hormone-simulated pregnancy (HSP). Additionally, immobility that is increased by FST pre-exposure is not readily prevented by treatment with standard antidepressant medications in postpartum females. Depressionlike behaviors previously observed in females that have undergone HSP may result from the more dramatic changes in estradiol, prolactin or corticosterone that occur during the early "postpartum" period, compared to the more subtle changes in these hormones that occur in actual postpartum females.Keywords postpartum depression; females; antidepressants; forced swim test; gestational stress; estradiol; prolactin; corticosterone; pregnancy; nominfensine; sertraline; desipramine Previous studies suggest that hormonal changes that women undergo around the time of childbirth may trigger postpartum mood disorders O'Hara, 2009;Parry et al., 2003). We and others have shown previously that ovariectomized female rats that have undergone hormone-simulated pregnancy (HSP) show depression-like behaviors during the "postpartum" period, suggesting that HSP followed by hormone withdrawal may be a useful animal model of postpartum depression (Galea et al., 2001;Green et al., 2009;Navarre et al., 2010;Stoffel and Craft, 2004). In these studies, the abrupt hormone withdrawal at the end of the HSP (modeling parturition) is considered to be the stressor; rats that have undergone HSP and are tested only once during the "postpartum" period on the forced swim test (FST) or
“…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 …”
“…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.…”
Section: Perinatal Exposure To Ssris and Neural Development: Preclinimentioning
confidence: 99%
“…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].…”
Section: Preclinical Studies On Perinatal Ssri Effects In the Absencementioning
confidence: 99%
“…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.…”
Section: Preclinical Studies On Perinatal Ssri Effects In the Absencementioning
Selective serotonin reuptake inhibitor (SSRI) medications are the most common antidepressant treatment used during pregnancy and the postpartum period. Up to 10% of pregnant women are prescribed SSRIs. Serotonin plays an integral part in neurodevelopment, and questions have been raised about the placental transfer of SSRIs and the effects of preventing reuptake of presynaptic serotonin on fetal neurodevelopment. Preclinical data is beginning to document a role of early exposure to SSRIs in long-term developmental outcomes related to a number of brain regions, such as the hippocampus, cortex and cerebellum. To date, the majority of preclinical work has investigated the developmental effects of SSRIs in the offspring of healthy mothers; however, more research is needed on the effects of these medications in the face of maternal adversity. This minireview will highlight emerging evidence from clinical and preclinical studies investigating the impact of perinatal SSRI exposure on brain development and neural plasticity.
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