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The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation

Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine—a muscarinic receptor (mAChR) agonist—displ...

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Autores principales: Hoeller, Alexandre A., Costa, Ana Paula R., Bicca, Maíra A., Matheus, Filipe C., Lach, Gilliard, Spiga, Francesca, Lightman, Stafford L., Walz, Roger, Collingridge, Graham L., Bortolotto, Zuner A., de Lima, Thereza C. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721870/
https://www.ncbi.nlm.nih.gov/pubmed/26795565
http://dx.doi.org/10.1371/journal.pone.0147293
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author Hoeller, Alexandre A.
Costa, Ana Paula R.
Bicca, Maíra A.
Matheus, Filipe C.
Lach, Gilliard
Spiga, Francesca
Lightman, Stafford L.
Walz, Roger
Collingridge, Graham L.
Bortolotto, Zuner A.
de Lima, Thereza C. M.
author_facet Hoeller, Alexandre A.
Costa, Ana Paula R.
Bicca, Maíra A.
Matheus, Filipe C.
Lach, Gilliard
Spiga, Francesca
Lightman, Stafford L.
Walz, Roger
Collingridge, Graham L.
Bortolotto, Zuner A.
de Lima, Thereza C. M.
author_sort Hoeller, Alexandre A.
collection PubMed
description Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine—a muscarinic receptor (mAChR) agonist—displayed persistent anxiogenic-like responses when evaluated in different behavioral tests and time-points (24 h up to 3 months later). Herein, we investigated whether the pilocarpine-induced long-term anxiogenesis modulates the HPA axis function and the putative involvement of NMDA receptors (NMDARs) following mAChRs activation. Accordingly, adult male Wistar rats presented anxiogenic-like behavior in the elevated plus-maze (EPM) after 24 h or 1 month of pilocarpine injection (150 mg/kg, i.p.). In these animals, mAChR activation disrupted HPA axis function inducing a long-term increase of corticosterone release associated with a reduced expression of hippocampal GRs, as well as consistently decreased NMDAR subunits expression. Furthermore, in another group of rats injected with memantine–an NMDARs antagonist (4 mg/kg, i.p.)–prior to pilocarpine, we found inhibition of anxiogenic-like behaviors in the EPM but no further alterations in the pilocarpine-induced NMDARs downregulation. Our data provide evidence that behavioral anxiogenesis induced by mAChR activation effectively yields short- and long-term alterations in hippocampal NMDARs expression associated with impairment of hippocampal inhibitory regulation of HPA axis activity. This is a novel mechanism associated with anxiety-like responses in rats, which comprise a putative target to future translational studies.
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spelling pubmed-47218702016-01-30 The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation Hoeller, Alexandre A. Costa, Ana Paula R. Bicca, Maíra A. Matheus, Filipe C. Lach, Gilliard Spiga, Francesca Lightman, Stafford L. Walz, Roger Collingridge, Graham L. Bortolotto, Zuner A. de Lima, Thereza C. M. PLoS One Research Article Extensive evidence indicates the influence of the cholinergic system on emotional processing. Previous findings provided new insights into the underlying mechanisms of long-term anxiety, showing that rats injected with a single systemic dose of pilocarpine—a muscarinic receptor (mAChR) agonist—displayed persistent anxiogenic-like responses when evaluated in different behavioral tests and time-points (24 h up to 3 months later). Herein, we investigated whether the pilocarpine-induced long-term anxiogenesis modulates the HPA axis function and the putative involvement of NMDA receptors (NMDARs) following mAChRs activation. Accordingly, adult male Wistar rats presented anxiogenic-like behavior in the elevated plus-maze (EPM) after 24 h or 1 month of pilocarpine injection (150 mg/kg, i.p.). In these animals, mAChR activation disrupted HPA axis function inducing a long-term increase of corticosterone release associated with a reduced expression of hippocampal GRs, as well as consistently decreased NMDAR subunits expression. Furthermore, in another group of rats injected with memantine–an NMDARs antagonist (4 mg/kg, i.p.)–prior to pilocarpine, we found inhibition of anxiogenic-like behaviors in the EPM but no further alterations in the pilocarpine-induced NMDARs downregulation. Our data provide evidence that behavioral anxiogenesis induced by mAChR activation effectively yields short- and long-term alterations in hippocampal NMDARs expression associated with impairment of hippocampal inhibitory regulation of HPA axis activity. This is a novel mechanism associated with anxiety-like responses in rats, which comprise a putative target to future translational studies. Public Library of Science 2016-01-21 /pmc/articles/PMC4721870/ /pubmed/26795565 http://dx.doi.org/10.1371/journal.pone.0147293 Text en © 2016 Hoeller 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
Hoeller, Alexandre A.
Costa, Ana Paula R.
Bicca, Maíra A.
Matheus, Filipe C.
Lach, Gilliard
Spiga, Francesca
Lightman, Stafford L.
Walz, Roger
Collingridge, Graham L.
Bortolotto, Zuner A.
de Lima, Thereza C. M.
The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title_full The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title_fullStr The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title_full_unstemmed The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title_short The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation
title_sort role of hippocampal nmda receptors in long-term emotional responses following muscarinic receptor activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721870/
https://www.ncbi.nlm.nih.gov/pubmed/26795565
http://dx.doi.org/10.1371/journal.pone.0147293
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