Fluoxetine exposure during pregnancy and lactation: Effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Oliveira, José Fernando de; Ponte, Bianca; Barbosa, Ana Paula Moreno; Veríssimo, Luiz Fernando; Gomes, M.V.; Pelosi, Gislaine Garcia; Britto, Luiz Roberto Giorgetti de; Moreira, Estefânia Gastaldello

doi:10.1016/j.bbr.2013.05.064

Cited by 45 publications

(22 citation statements)

References 60 publications

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“…For instance, maternal postpartum fluoxetine diminished hippocampal glucocorticoid receptor density in adolescent male but not female rat offspring (Pawluski et al, 2012c). Additionally, maternal fluoxetine during gestation and lactation enhanced activation (Fos expression) in the basolateral amygdala and medial amygdala after restraint stress in adult female but not male rat offspring (Francis-Oliveira et al, 2013). Both the hippocampus and amygdala are sources of limbic control over the HPA axis (reviewed in Herman and Cullinan, 1997) and could therefore contribute to differences in HPA axis negative feedback.…”

Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated mentioning

confidence: 97%

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

et al. 2016

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Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.

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Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated mentioning

confidence: 97%

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

et al. 2016

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“…5-HT system modulation at an early age is not clinically irrelevant, as the serotonin reuptake inhibitor is widely used for the treatment of depressive disorders in women during pregnancy and in the postpartum period. Some authors demonstrate that Fx can cross human placenta and its presence in breast milk could induce harmful effects on developing fetuses and newborns [15,16]; thus, the evaluation of the hemodynamics and oxidative status in brainstem and heart in adult animal could provide further insight into serotonin modulation at a critical period of development. Thus, the aim of the present study was to investigate whether serotonin system manipulation by Fx treatment, during development, would affect hemodynamic response and oxidative metabolism in brainstem and heart in adult rat.…”

Section: Introductionmentioning

confidence: 99%

Serotonin modulation in neonatal age does not impair cardiovascular physiology in adult female rats: Hemodynamics and oxidative stress analysis

et al. 2016

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“…In one, female offspring exposed to FLX by non-stressful maternal administration showed decreased anxiety in the EPM, though not in the OFT [36]. In the other, adolescent, but not adult, male and female rats exposed to FLX from gestation through to weaning showed decreased anxiety in the novelty-suppressed feeding test [47]. There do not appear to be any obviously identifiable experimental factors that can account for these disparate findings.…”

Section: Long-term Behavioural Outcomesmentioning

confidence: 99%

“…The effects of FLX exposure on stress responsivity also extend beyond the hippocampus, as decreased serum corticosterone and a decrease in the free corticosterone index have also been noted, again only in males [65]. Additionally, FLX exposure appears to alter activation of certain regions of the brain in response to restraint stress, with adolescent males showing less activation of the basolateral amygdala, and adult males showing less activation of both the basolateral and medial regions of the amygdala [47]. None of these changes were observed in females, nor was activity in the central nucleus of the amygdala or the paraventricular nucleus altered in either sex.…”

Section: Neuroanatomical Outcomesmentioning

confidence: 99%

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

2013

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During and following pregnancy, women are at high risk of experiencing depression, for which fluoxetine (FLX; brand names Prozac, Sarafem, Rapiflux) is the most commonly prescribed treatment. An estimated 1.4-2.1% of pregnant women use this medication, which inhibits the reuptake of serotonin and thereby increases serotonergic activity at the synapse. Serotonin acts as a cue guiding numerous neurodevelopmental processes, and changes in the concentration of serotonin can disrupt normal in utero brain development and organization in humans and other animals, thus providing a mechanism by which maternal intake of FLX might alter neural development and ultimately behaviour. Despite this possibility, long-term alterations of behaviour and the brain have not been well studied in individuals exposed to FLX during pregnancy or soon after birth, perhaps because conducting such studies beyond infancy presents significant challenges. To remedy this problem, many researchers have turned to modelling the effects of developmental FLX exposure in non-human animals, primarily rodents. The body of literature on this topic has expanded considerably over the past several years, yet a comprehensive review is lacking. In order to fill this gap, we have summarized the findings of those studies describing the long-term behavioural and neurophysiological effects of FLX exposure in non-human animals in early development. We also discuss methodological considerations and common shortcomings of research in this area. The precise nature of the long-term effects of developmental FLX exposure remains difficult to specify, as these effects appear to be highly variable and dependent on numerous factors. Overall, however, it is clear that early FLX exposure in non-human animals can alter the development of the brain in ways that are relevant to behaviour in adulthood, decreasing exploration and social interaction, and in some cases altering anxiety- and depression-like behaviours.

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Fluoxetine exposure during pregnancy and lactation: Effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Cited by 45 publications

References 60 publications

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Serotonin modulation in neonatal age does not impair cardiovascular physiology in adult female rats: Hemodynamics and oxidative stress analysis

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

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