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--dis...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4721870?pdf=render |
id |
doaj-74193c75db8b4c83b457f3e3d9109324 |
---|---|
record_format |
Article |
spelling |
doaj-74193c75db8b4c83b457f3e3d91093242020-11-24T21:41:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014729310.1371/journal.pone.0147293The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation.Alexandre A HoellerAna Paula R CostaMaíra A BiccaFilipe C MatheusGilliard LachFrancesca SpigaStafford L LightmanRoger WalzGraham L CollingridgeZuner A BortolottoThereza C M de LimaExtensive 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.http://europepmc.org/articles/PMC4721870?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandre A Hoeller Ana Paula R Costa Maíra A Bicca Filipe C Matheus Gilliard Lach Francesca Spiga Stafford L Lightman Roger Walz Graham L Collingridge Zuner A Bortolotto Thereza C M de Lima |
spellingShingle |
Alexandre A Hoeller Ana Paula R Costa Maíra A Bicca Filipe C Matheus Gilliard Lach Francesca Spiga Stafford L Lightman Roger Walz Graham L Collingridge Zuner A Bortolotto Thereza C M de Lima The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation. PLoS ONE |
author_facet |
Alexandre A Hoeller Ana Paula R Costa Maíra A Bicca Filipe C Matheus Gilliard Lach Francesca Spiga Stafford L Lightman Roger Walz Graham L Collingridge Zuner A Bortolotto Thereza C M de Lima |
author_sort |
Alexandre A Hoeller |
title |
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_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_sort |
role of hippocampal nmda receptors in long-term emotional responses following muscarinic receptor activation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
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. |
url |
http://europepmc.org/articles/PMC4721870?pdf=render |
work_keys_str_mv |
AT alexandreahoeller theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT anapaularcosta theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT mairaabicca theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT filipecmatheus theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT gilliardlach theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT francescaspiga theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT staffordllightman theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT rogerwalz theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT grahamlcollingridge theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT zunerabortolotto theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT therezacmdelima theroleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT alexandreahoeller roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT anapaularcosta roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT mairaabicca roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT filipecmatheus roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT gilliardlach roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT francescaspiga roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT staffordllightman roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT rogerwalz roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT grahamlcollingridge roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT zunerabortolotto roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation AT therezacmdelima roleofhippocampalnmdareceptorsinlongtermemotionalresponsesfollowingmuscarinicreceptoractivation |
_version_ |
1725921995042848768 |