Perinatal SSRI medications and offspring hippocampal plasticity: interaction with maternal stress and sex

Pawluski, Jodi L.; Gemmel, Mary

doi:10.1007/s42000-018-0011-y

Cited by 18 publications

(14 citation statements)

References 89 publications

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“…However, several studies did find alterations in the brain as a result of perinatal SSRI exposure or maternal stress. To name a few, alterations were found in offspring's hippocampal 5-HT levels, it's metabolite 5-hydroxyindolacetic acid, the serotonergic transmission, the serotonin transporter gene expression and the 5-HT turnover (reviewed in [78]). Outside the serotonergic system, also long-term hippocampal plasticity effects of perinatal SSRIs have been reported, including changes in the expression of the brain-derived neurotrophic factor (BDNF [53];) and the epigenetic regulation of the BDNF gene [44,56].…”

Section: Limitationsmentioning

confidence: 99%

“…More hippocampal effects have been reported (e.g. for review, see [78]), and several other brain areas may play a role in the alterations found in the behavioral outcomes of the offspring as well. Similar alterations could have occurred in the offspring exposed to fluoxetine and/or maternal adversity in the rats described in the current study but this assumption is speculative, and the study of underlying mechanisms was beyond the scope of this study.…”

Section: Limitationsmentioning

confidence: 99%

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Perinatal fluoxetine treatment and dams’ early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex

Houwing

Schuttel

Struik

et al. 2020

Behavioural Brain Research

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Many women diagnosed with a major depression continue or initiate antidepressant treatment during pregnancy. Both maternal stress and selective serotonin inhibitor (SSRI) antidepressant treatment during pregnancy have been associated with changes in offspring behavior, including increased anxiety and depressive-like behavior. Our aim was to investigate the effects of the SSRI fluoxetine (FLX), with and without the presence of a maternal depression, on affective behavior in male and female rat offspring. As reduced serotonin transporter (SERT) availability has been associated with altered behavioral outcome, both offspring with normal (SERT +/+ ) and reduced (SERT +/− ) SERT expression were included. For our animal model of maternal depression, SERT +/ − dams exposed to early life stress were used. Perinatal FLX treatment and early life stress in dams (ELSD) had sex-and genotype-specific effects on affective behavior in the offspring. In female offspring, perinatal FLX exposure interacted with SERT genotype to increase anxiety and depressive-like behavior in SERT +/+ , but not SERT +/− , females. In male offspring, ELSD reduced anxiety and interacted with SERT genotype to decrease depressive-like behavior in SERT +/− , but not SERT +/+ , males. Altogether, SERT +/+ female offspring appear to be more sensitive than SERT +/− females to the effects of perinatal FLX exposure, while SERT +/− male offspring appear more sensitive than SERT +/+ males to the effects of ELSD on affective behavior. Our data suggest a role for offspring SERT genotype and sex in FLX and ELSD-induced effects on affective behavior, thereby contributing to our understanding of the effects of perinatal SSRI treatment on offspring behavior later in life.

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Section: Limitationsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Perinatal fluoxetine treatment and dams’ early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex

Houwing

Schuttel

Struik

et al. 2020

Behavioural Brain Research

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“…It is, however, also able to alter developmental mechanisms and behaviors without counteracting prenatal stress; similar to the human study of Rotem-Kohave et al [145]. That both gestational SSRI exposure and prenatal stress can influence brain development independent of each other is also highlighted in another review focusing specifically on hippocampal plasticity [203].…”

Section: Maternal Ssri Intake Affects Animal Offspring 5-ht Signalingmentioning

confidence: 63%

“…That perinatal SSRI exposure, irrespective of prenatal stress, can impact the HPA-axis has been shown in other studies as well. Perinatal fluoxetine resulted in increased serum corticosteroid binding globulin, decreased hippocampal synaptic protein (PSD-95), reduced glucocorticoid receptor density in the hippocampus, and reduced glucocorticoid receptor density in the mPFC [150,160,203,237].…”

Section: Maternal Ssri Intake Affects Animal Offspring's Brain Circuimentioning

confidence: 99%

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Hanswijk

Spoelder

Shan

et al. 2020

IJMS

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Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.

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“…Neuroanatomical and functional connections among these structures determine the integration of nociceptive and affective signals and the involvement of the descending serotonergic system that regulates nociceptive signals in pain and depressive behaviors (Chaouloff, 2000). Since 5-HT1AR is involved in nociception (Granados-Soto et al, 2010) and psycho-emotional behavior (Savitz et al, 2009), changes in its activity in the prenatal period may manifest itself later in alteration of various types of adaptive behaviors (Knaepen et al, 2013, 2014; Kiryanova et al, 2017, 2018; Pawluski and Gemmel, 2018).…”

Section: Introductionmentioning

confidence: 99%

Differences Between the Prenatal Effects of Fluoxetine or Buspirone Alone or in Combination on Pain and Affective Behaviors in Prenatally Stressed Male and Female Rats

Butkevich

Mikhailenko

Vershinina

et al. 2019

Front. Behav. Neurosci.

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The selective serotonin reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone are used to treat depression and anxiety. Previously we demonstrated that chronic stress during pregnancy (prenatal stress) in rats, used as a model of maternal depression risk, increased inflammatory pain and depressive-like behavior in the offspring; buspirone injected to pregnant dams was protective. Clinically, the addition of buspirone to fluoxetine increases the latter’s efficacy in treating depression in patients. Here, we investigated the influence of repeated prenatal injections of fluoxetine, buspirone or their combination on pain- and depressive-like behaviors in prenatally stressed young male and female rats. Prenatal stress augmented depressive-like behavior and both thermal and inflammatory pain (formalin test), replicating our prior findings, and increased basal levels of corticosterone in the blood plasma. Both drugs and their combination reduced the effects of prenatal stress on thermal pain and depressive-like behavior independently of sex. The combination of fluoxetine and buspirone, compared with fluoxetine, was more antinociceptive in the hot plate test in both sexes, and when compared with buspirone, was more antinociceptive only in males. A detailed study of the time-course of formalin-induced pain showed a nuanced effect of these drugs that was sex-dependent. The combination of the two drugs was less effective in females than males during the initial acute phase of nociceptive behavior in flexing + shaking behaviors, whereas that combination was more effective than fluoxetine alone in the first acute phase of licking behavior in females. The antinociceptive effect of buspirone dominated that of the drug combination and of fluoxetine alone, especially during the interphase of the formalin test in both sexes for both flexing + shaking and licking, suggesting a more effective prenatal action of buspirone on the development of a descending serotonergic inhibitory system modulating pain in the spinal cord dorsal horn neurons. Our results indicate that inflammatory pain-like responses integrated at the spinal level in males were more vulnerable to prenatal stress than females. In licking, the antinociceptive effect of fluoxetine and drug combination in the interphase was more in males than females. The data underscore the importance of considering sexual dimorphism when using drug therapy.

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Perinatal SSRI medications and offspring hippocampal plasticity: interaction with maternal stress and sex

Cited by 18 publications

References 89 publications

Perinatal fluoxetine treatment and dams’ early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex

Perinatal fluoxetine treatment and dams’ early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Differences Between the Prenatal Effects of Fluoxetine or Buspirone Alone or in Combination on Pain and Affective Behaviors in Prenatally Stressed Male and Female Rats

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