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Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

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Abstract

Rationale

During pregnancy and postpartum period, 20 % of women are affected by depression, which is a growing health concern. Selective serotonin reuptake inhibitor (SSRI) medications are popular treatments for maternal depression; however, the effect of maternal depression and perinatal SSRI exposure on offspring’s neural development needs further investigation.

Objectives

This study aims to determine the role of developmental fluoxetine exposure on hippocampal plasticity in the adult offspring.

Methods

Sprague-Dawley rat offspring were exposed to fluoxetine beginning on postnatal day 1. Offspring were also exposed to prenatal maternal stress. Four groups of male and female offspring were used: (1) prenatal stress + fluoxetine, (2) prenatal stress + vehicle, (3) fluoxetine alone, and (4) vehicle alone. Hippocampi were analyzed for levels of cell proliferation, immature neurons, and new cell survival (3 weeks after 5-bromo-2-deoxyuridine injection) in the granule cell layer, as well as synaptophysin density in the CA3 region and granule cell layer. TPH staining was assessed in the dorsal raphe nucleus.

Results

Developmental fluoxetine exposure to prenatally stressed offspring reversed the effect of prenatal stress or fluoxetine exposure alone on the number of immature neurons. Prenatal stress alone, regardless of developmental exposure to fluoxetine, markedly decreased hippocampal cell proliferation and tended to decrease new cell survival. Furthermore, in adult female offspring, developmental fluoxetine exposure greatly increased new cell survival and significantly decreased synaptophysin density in the granule cell layer.

Conclusions

There are long-term effects of developmental SSRI exposure on hippocampal plasticity that is differentially affected by expose to maternal adversity and offspring sex.

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Acknowledgements of funding

JLP presently holds a Chargé de Recherche position with Fonds de la Recherche Scientifique at the GIGA-Neurosciences, University of Liège, Belgium. The experiments comply with the current laws of the Netherlands, the country in which the experiments were performed.

Conflict of interest

The authors have no conflict of interest to report.

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Authors and Affiliations

  1. School for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands

    Ine Rayen, Harry W. M. Steinbusch & Jodi L. Pawluski

  2. Department of Biological Sciences, Ohio University, Athens, OH, USA

    Mary Gemmel, Grace Pauley & Jodi L. Pawluski

  3. GIGA-Neurosciences, University of Liège, 1 Avenue de l’Hôpital (Bat. B36), Liège, Belgium, 4000

    Jodi L. Pawluski

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  1. Ine Rayen
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  2. Mary Gemmel
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  3. Grace Pauley
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  4. Harry W. M. Steinbusch
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  5. Jodi L. Pawluski
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Correspondence to Jodi L. Pawluski.

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Rayen, I., Gemmel, M., Pauley, G. et al. Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity. Psychopharmacology 232, 1231–1244 (2015). https://doi.org/10.1007/s00213-014-3758-0

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  • DOI: https://doi.org/10.1007/s00213-014-3758-0

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