Maternal separation induces anhedonia in female heterozygous serotonin transporter knockout rats

Houwing, Danielle J.; Ramsteijn, Anouschka S.; Riemersma, Iris; Olivier, Jocelien

doi:10.1016/j.bbr.2018.08.031

Cited by 24 publications

(30 citation statements)

References 23 publications

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“…In adulthood, sMV females show a depressive-like phenotype, reflected in a lower sucrose preference and lower neural growth factor gene expression than cMV females. 42 We treated sMV and cMV rats dams daily with fluoxetine (FLX), a commonly used SSRI, or vehicle (Veh) throughout pregnancy and lactation. Weekly fecal samples were collected for 16S rRNA gene sequencing.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

et al. 2020

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Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear. We studied this using a rat model relevant to depression, where adult females with a genetic vulnerability and stressed as pups show depressive-like behaviors. Throughout pregnancy and lactation, females received the SSRI fluoxetine or vehicle. High-resolution 16S ribosomal RNA marker gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Not surprisingly, we found that pregnancy and lactation segregate in terms of fecal microbiome diversity and composition, accompanied by changes in metabolite availability. However, we also showed that fluoxetine treatment altered important features of this transition from pregnancy to lactation most clearly in previously stressed dams, with lower fecal amino acid concentrations. Amino acid concentrations, in turn, correlated negatively with the relative abundance of bacterial taxa such as Prevotella and Bacteroides. Our study demonstrates an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in a rat model relevant to depression, possibly through parallel changes in the gut microbiome. Since microbial metabolites contribute to homeostasis and development, insults to the maternal microbiome by SSRIs might have health consequences for mother and offspring.

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Section: Introductionmentioning

confidence: 99%

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

et al. 2020

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“…Thus, dysregulation of the HPA axis may be a marker of vulnerability to anxiety [48], where the HPA axis may be affected by the postnatal adversity induced by maternal separation [52]. Furthermore, 4-8 h maternal separation from 2 to 21 PND in male C57BL/6 mice increases anxiety-like behaviors in social preference test and in the elevated plus maze (reduction of time spent into open arms), which was related to an increase in IL-1β in the hippocampus, PFC, and serum [53].…”

Section: Anxiety Animal Modelsmentioning

confidence: 99%

Neuropharmacology of Anxiety Disorders at Young Age: A Perspective from Preclinical Research

Guillén-Ruiz¹,

Bernal-Morales²,

Soria-Fregozo³

et al. 2020

Behavioral Pharmacology - From Basic to Clinical Research

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Anxiety is one of the most common psychopathologies in the general population that often begin early in life; however, research on this disorder during early developmental stages has been poorly explored compared to adults. A better understanding of the anxiety disorder through childhood is essential to develop more effective treatments. This chapter provides a general overview of the usefulness of animal models of childhood anxiety and its neurobiological bases to discuss how the studies on animals meet the several criteria of validity to discover pathophysiological mechanisms of human disorders and new treatments for these conditions. The research methodology for this chapter consisted in using a thesaurus system such as Medical Subject Headings (MeSH) terms of the National Library of Medicine to find original articles in databases as PubMed or Web of Science about preclinical findings related to the neuropharmacology of anxiety before adulthood. The contribution of this chapter is to provide data from preclinical studies which are encouraged to a better comprehension of anxiety at young age.

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“…SERT +/female rats (MV) were exposed to adversity in the form of early life stress (sMV) to induce anhedonia 62,66 . The early life stress protocol was conducted as previously described 65 .…”

Section: Maternal Adversity and Fluoxetine Treatmentmentioning

confidence: 99%

“…MV females show a depressive-like phenotype in adulthood after being exposed to early life stress (sMV). This is reflected in anhedonic behavior and lower central neural growth factor gene expression in sMVthan in control (cMV) females 62 . We treated sMV and cMV dams daily with fluoxetine (FLX), a commonly used SSRI, or vehicle (Veh) from the start of gestation until weaning at postnatal day (PND)21 of the pups.…”

Section: Introductionmentioning

confidence: 99%

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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Maternal separation induces anhedonia in female heterozygous serotonin transporter knockout rats

Cited by 24 publications

References 23 publications

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

Neuropharmacology of Anxiety Disorders at Young Age: A Perspective from Preclinical Research

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

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