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Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment
The male germ line is capable of transmitting a legacy of stress exposure to the next generation of offspring. This transgenerational process manifests by altering offspring affective behaviours, cognition and metabolism. Paternal early life trauma causes hippocampal serotonergic dysregulation in ma...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054191/ https://www.ncbi.nlm.nih.gov/pubmed/30046455 http://dx.doi.org/10.1093/eep/dvy015 |
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author | Rawat, Arina Guo, Jackey Renoir, Thibault Pang, Terence Y Hannan, Anthony J |
author_facet | Rawat, Arina Guo, Jackey Renoir, Thibault Pang, Terence Y Hannan, Anthony J |
author_sort | Rawat, Arina |
collection | PubMed |
description | The male germ line is capable of transmitting a legacy of stress exposure to the next generation of offspring. This transgenerational process manifests by altering offspring affective behaviours, cognition and metabolism. Paternal early life trauma causes hippocampal serotonergic dysregulation in male offspring. We previously showed a transgenerational modification to male offspring anxiety-like behaviours by treatment of adult male breeders with corticosterone (CORT) prior to mating. In the present study, we used offspring from our paternal CORT model and characterised offspring serotonergic function by examining their responses to the 5HT(1A)R agonist, 8-OH-DPAT, and the selective serotonin reuptake inhibitor, sertraline. We also examined whether post-weaning environmental enrichment, a paradigm well-known to modulate serotonergic signalling in the brain, had the capacity to normalise the anxiety phenotype of male offspring. Finally, we assessed gene expression levels of 5HT(1A)R and serotonin transporter in the offspring hippocampus to determine whether deficits in gene transcription contributed to the male-only anxiety phenotype. We report that male and female offspring of CORT-treated fathers are hypersensitive to sertraline but have normal hypothermic responses to 8-OH-DPAT. No deficits in htr1a and sert were found in association with paternal CORT treatment, and environmental enrichment did not rescue the anxiety phenotype of male offspring on the elevated-plus maze. These findings indicate that varying forms of paternal stress exert different effects on offspring brain serotonergic function. |
format | Online Article Text |
id | pubmed-6054191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60541912018-07-25 Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment Rawat, Arina Guo, Jackey Renoir, Thibault Pang, Terence Y Hannan, Anthony J Environ Epigenet Research Article The male germ line is capable of transmitting a legacy of stress exposure to the next generation of offspring. This transgenerational process manifests by altering offspring affective behaviours, cognition and metabolism. Paternal early life trauma causes hippocampal serotonergic dysregulation in male offspring. We previously showed a transgenerational modification to male offspring anxiety-like behaviours by treatment of adult male breeders with corticosterone (CORT) prior to mating. In the present study, we used offspring from our paternal CORT model and characterised offspring serotonergic function by examining their responses to the 5HT(1A)R agonist, 8-OH-DPAT, and the selective serotonin reuptake inhibitor, sertraline. We also examined whether post-weaning environmental enrichment, a paradigm well-known to modulate serotonergic signalling in the brain, had the capacity to normalise the anxiety phenotype of male offspring. Finally, we assessed gene expression levels of 5HT(1A)R and serotonin transporter in the offspring hippocampus to determine whether deficits in gene transcription contributed to the male-only anxiety phenotype. We report that male and female offspring of CORT-treated fathers are hypersensitive to sertraline but have normal hypothermic responses to 8-OH-DPAT. No deficits in htr1a and sert were found in association with paternal CORT treatment, and environmental enrichment did not rescue the anxiety phenotype of male offspring on the elevated-plus maze. These findings indicate that varying forms of paternal stress exert different effects on offspring brain serotonergic function. Oxford University Press 2018-07-19 /pmc/articles/PMC6054191/ /pubmed/30046455 http://dx.doi.org/10.1093/eep/dvy015 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Rawat, Arina Guo, Jackey Renoir, Thibault Pang, Terence Y Hannan, Anthony J Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title | Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title_full | Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title_fullStr | Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title_full_unstemmed | Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title_short | Hypersensitivity to sertraline in the absence of hippocampal 5-HT(1A)R and 5-HTT gene expression changes following paternal corticosterone treatment |
title_sort | hypersensitivity to sertraline in the absence of hippocampal 5-ht(1a)r and 5-htt gene expression changes following paternal corticosterone treatment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054191/ https://www.ncbi.nlm.nih.gov/pubmed/30046455 http://dx.doi.org/10.1093/eep/dvy015 |
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