<i>In Utero</i> Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development

Velasquez, Juan C.; Zhao, Qiuying; Chan, Yu-Chang; Galindo, Lígia Cristina Monteiro; Simasotchi, Christelle; Wu, Dan; Hou, Zhipeng; Herod, Skyla M.; Oberlander, Tim F.; Gil, Sophie; Fournier, Thierry; Burd, Irina; Andrews, Anne M.; Bonnin, Alexandre

doi:10.1021/acschemneuro.9b00180

Cited by 17 publications

(26 citation statements)

References 65 publications

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“…Since the fights were not sufficient to expose enough rats to both instances, we continued the search for aggressive encounters until most rats had played both roles at least once. This resulted in an outcome of [5][6] fights per rat at baseline, and 5-7 fights in post-stress. However, some rats never played both roles during the encounters, which resulted in a few missing data points.…”

Section: Behavioral Observationsmentioning

confidence: 99%

“…Selective serotonin reuptake inhibitors (SSRIs) are the most prevalent treatment for women with depression during pregnancy [1,2]. Nonetheless, since SSRIs can cross the placenta and appear in breastmilk [3][4][5], the question rises how this treatment might affect the developing fetus. SSRI exposure during development affects the serotoninergic system in the fetus [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

Heinla

Heijkoop

Houwing

et al. 2019

Preprint

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AbstractSSRIs are commonly used to treat pregnant women with depression. However, SSRIs can cross the placenta and affect the development of the fetus. The effects of perinatal SSRI exposure, and especially the effects on social behavior, are still incompletely documented. This study first aims to investigate whether rats show prosocial behavior in the form of consolation behavior. Secondly, it aims to investigate whether perinatal SSRI exposure affects this prosocial behavior. At last, we investigate whether the behavior changed after the rats had been exposed to an additional white-noise stressor.Rat dams received 10 mg/kg/d fluoxetine (FLX) or vehicle (CTR) via oral gavage from gestational day 1 until postnatal day 21. At adulthood, the rat offspring were housed in four cohorts of 4 females and 4 males in a seminatural environment. As prosocial behaviors are more prominent after stressful situations, we investigated the behavioral response of rats immediately after natural aggressive encounters (fights). Additionally, we studied whether a stressful white-noise exposure would alter this response to the aggressive encounters.Our study indicates that CTR-female rats are able to show third party prosocial behavior in response to witnessing aggressive encounters between conspecifics in a seminatural environment. In addition, we showed that perinatal FLX exposure impairs the display of prosocial behavior in female rats. Moreover, we found no signs of prosocial behavior in CTR- and FLX-males after natural aggressive encounters. After white-noise exposure the effects in third party prosocial behavior of CTR-females ceased to exist. We conclude that female rats are able to show prosocial behavior, possibly in the form of consolation behavior. In addition, the negative effects of perinatal fluoxetine exposure on prosocial behavior could provide additional evidence that SSRI treatment during pregnancy could contribute to the risk for social impairments in the offspring.

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Section: Behavioral Observationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

Heinla

Heijkoop

Houwing

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Although the mechanism behind this is not clear, other work suggests that perinatal SSRI exposure is indeed capable of preventing some of the adverse effects of maternal adversity. For example, in utero citalopram exposure normalized the increased fetal frontal cortex serotonin levels induced by chronic prenatal stress 53 . Similarly, perinatal fluoxetine exposure largely prevented the effects of pre-gestational maternal stress on increased serotonin levels in the PFC in pre-adolescent offspring 49 , and stress coping behavior and hippocampal neurogenesis in adolescence 54 .…”

Section: Myelination Of Axons By Oligodendrocytes Plays a Critical Romentioning

confidence: 99%

“…Lastly, we advocate for continued cross-talk between animal and human studies. For example, imaging techniques in rodents can provide a link between (pre)clinical molecular studies and human neuroimaging findings 46,53 . Figure 1: Overview of study design.…”

Section: Myelination Of Axons By Oligodendrocytes Plays a Critical Romentioning

confidence: 99%

“…Sex-specificity is often seen for neurodevelopmental outcomes after both perinatal SSRI exposure [49][50][51] and prenatal stress 49,52 . Interestingly, perinatal SSRI exposure might reverse some of the neurodevelopmental effects of maternal (pre)gestational stress, such as altered brain serotonin levels 49,53 and stress-coping behavior 54 .…”

Section: Introductionmentioning

confidence: 99%

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Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

Ramsteijn

Verkaik-Schakel

Houwing

et al. 2020

Preprint

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Many pregnant women experience symptoms of depression, and are often treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine. In utero exposure to SSRIs and maternal depressive symptoms is associated with sex-specific effects on the brain and behavior. However, knowledge about the neurobiological mechanisms underlying these sex differences is limited. In addition, most animal research into developmental SSRI exposure neglects the influence of maternal adversity. Therefore, we used a rat model relevant to depression to investigate the molecular effects of perinatal fluoxetine exposure in male and female juvenile offspring. We performed RNA sequencing and targeted DNA methylation analyses on the prefrontal cortex and basolateral amygdala; key regions of the corticolimbic circuit. Perinatal fluoxetine enhanced myelin-related gene expression in the prefrontal cortex, while inhibiting it in the basolateral amygdala. SSRI exposure and maternal adversity interacted to affect expression of genes such as myelin−associated glycoprotein (Mag) and myelin basic protein (Mbp). We speculate that altered myelination reflects altered brain maturation. In addition, these effects are stronger in males than in females, resembling known behavioral outcomes. Finally, Mag and Mbp expression correlated with DNA methylation, highlighting epigenetic regulation as a potential mechanism for developmental fluoxetine-induced changes in myelination.

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Antidepressants and Antipsychotics in Human Pregnancy: Transfer Across the Placenta and Opportunities for Modeling Studies

Zheng

Yang

Dallmann

2022

The Journal of Clinical Pharma

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There is limited information about the transfer of antidepressants and antipsychotics across the human placenta. The objective of the current review was to systematically screen the scientific literature using relevant keywords to collect quantitative data on placental transfer of these drugs in humans and to give an overview of current modeling approaches used in this context. The collected data encompassed clinically measured fetal:maternal (F:M) concentration ratios (ie, the ratio between drug concentrations measured in the umbilical cord and drug concentrations measured in the mother) and transfer data obtained from ex vivo cotyledon perfusion experiments. These data were found for 18 antidepressants and some of their pharmacologically active metabolites, and for 10 antipsychotics and the metabolites thereof. Based on the collected data, similar maternal and fetal exposure could be observed for only a few compounds (eg, norfluoxetine and desvenlafaxine), whereas for most drugs (eg, paroxetine, sertraline, and quetiapine), fetal exposure appeared to be on average lower than maternal exposure. Venlafaxine appeared to be an exception in that the data indicated equivalent or higher concentrations in the umbilical cord than in the mother. Physiologically based pharmacokinetic (PBPK) models were sporadically used to investigate maternal pharmacokinetics of antidepressants or antipsychotics (eg, for sertraline, aripiprazole, and olanzapine), although without explicitly addressing fetal drug exposure. It is recommended that PBPK modeling is applied more frequently to these drugs. Although no substitute for clinical studies, these tools can help to better understand pregnancy‐induced pharmacokinetic changes and ultimately contribute to a more evidence‐based pharmacotherapy of depression and psychosis in pregnant subjects.

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In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development

Cited by 17 publications

References 65 publications

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

Antidepressants and Antipsychotics in Human Pregnancy: Transfer Across the Placenta and Opportunities for Modeling Studies

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