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The effect of estrogenic compounds on psychosis-like behaviour in female rats

17β-estradiol treatment has shown benefit against schizophrenia symptoms, however long-term use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β-estradiol. An isomer of 17β-estra...

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Autores principales: Sbisa, Alyssa, van den Buuse, Maarten, Gogos, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868772/
https://www.ncbi.nlm.nih.gov/pubmed/29579065
http://dx.doi.org/10.1371/journal.pone.0193853
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author Sbisa, Alyssa
van den Buuse, Maarten
Gogos, Andrea
author_facet Sbisa, Alyssa
van den Buuse, Maarten
Gogos, Andrea
author_sort Sbisa, Alyssa
collection PubMed
description 17β-estradiol treatment has shown benefit against schizophrenia symptoms, however long-term use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β-estradiol. An isomer of 17β-estradiol, 17α-estradiol, is considered less carcinogenic, and non-feminising in males, however little is known about its potential as a treatment for schizophrenia. Moreover, the mechanism underlying the therapeutic action of estrogens remains unclear. We aimed to investigate the ability of these estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two acute pharmacologically-induced assays of psychosis-like behaviour: psychotomimetic drug-induced hyperlocomotion and disruption of prepulse inhibition (PPI). Female Long Evans rats were either intact, ovariectomised (OVX), or OVX and chronically treated with 17β-estradiol, 17α-estradiol, raloxifene or tamoxifen. Only 17β-estradiol treatment attenuated locomotor hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine. 17β-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine- and apomorphine (dopamine D1/D2 receptor agonist)-induced disruption of PPI. Raloxifene-treated rats showed attenuated apomorphine-induced PPI disruption only. Baseline PPI was significantly reduced following OVX, and this deficit was reversed by all estrogenic compounds. Further, PPI in OVX rats was increased following administration of apomorphine. This study confirms a protective effect of 17β-estradiol in two established animal models of psychosis, while tamoxifen showed beneficial effects against PPI disruption. In contrast, 17α-estradiol and raloxifene showed little effect on dopamine receptor-mediated psychosis-like behaviours. This study highlights the utility of some estrogenic compounds to attenuate psychosis-like behaviour in rats, supporting the notion that estrogens have therapeutic potential for psychotic disorders.
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spelling pubmed-58687722018-04-06 The effect of estrogenic compounds on psychosis-like behaviour in female rats Sbisa, Alyssa van den Buuse, Maarten Gogos, Andrea PLoS One Research Article 17β-estradiol treatment has shown benefit against schizophrenia symptoms, however long-term use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β-estradiol. An isomer of 17β-estradiol, 17α-estradiol, is considered less carcinogenic, and non-feminising in males, however little is known about its potential as a treatment for schizophrenia. Moreover, the mechanism underlying the therapeutic action of estrogens remains unclear. We aimed to investigate the ability of these estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two acute pharmacologically-induced assays of psychosis-like behaviour: psychotomimetic drug-induced hyperlocomotion and disruption of prepulse inhibition (PPI). Female Long Evans rats were either intact, ovariectomised (OVX), or OVX and chronically treated with 17β-estradiol, 17α-estradiol, raloxifene or tamoxifen. Only 17β-estradiol treatment attenuated locomotor hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine. 17β-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine- and apomorphine (dopamine D1/D2 receptor agonist)-induced disruption of PPI. Raloxifene-treated rats showed attenuated apomorphine-induced PPI disruption only. Baseline PPI was significantly reduced following OVX, and this deficit was reversed by all estrogenic compounds. Further, PPI in OVX rats was increased following administration of apomorphine. This study confirms a protective effect of 17β-estradiol in two established animal models of psychosis, while tamoxifen showed beneficial effects against PPI disruption. In contrast, 17α-estradiol and raloxifene showed little effect on dopamine receptor-mediated psychosis-like behaviours. This study highlights the utility of some estrogenic compounds to attenuate psychosis-like behaviour in rats, supporting the notion that estrogens have therapeutic potential for psychotic disorders. Public Library of Science 2018-03-26 /pmc/articles/PMC5868772/ /pubmed/29579065 http://dx.doi.org/10.1371/journal.pone.0193853 Text en © 2018 Sbisa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sbisa, Alyssa
van den Buuse, Maarten
Gogos, Andrea
The effect of estrogenic compounds on psychosis-like behaviour in female rats
title The effect of estrogenic compounds on psychosis-like behaviour in female rats
title_full The effect of estrogenic compounds on psychosis-like behaviour in female rats
title_fullStr The effect of estrogenic compounds on psychosis-like behaviour in female rats
title_full_unstemmed The effect of estrogenic compounds on psychosis-like behaviour in female rats
title_short The effect of estrogenic compounds on psychosis-like behaviour in female rats
title_sort effect of estrogenic compounds on psychosis-like behaviour in female rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868772/
https://www.ncbi.nlm.nih.gov/pubmed/29579065
http://dx.doi.org/10.1371/journal.pone.0193853
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