An animal model of emotional blunting in schizophrenia.

Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fe...

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Main Authors: Charmaine Y Pietersen, Fokko J Bosker, Janine Doorduin, Minke E Jongsma, Folkert Postema, Joseph V Haas, Michael P Johnson, Tineke Koch, Tony Vladusich, Johan A den Boer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2137950?pdf=render
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author Charmaine Y Pietersen
Fokko J Bosker
Janine Doorduin
Minke E Jongsma
Folkert Postema
Joseph V Haas
Michael P Johnson
Tineke Koch
Tony Vladusich
Johan A den Boer
author_facet Charmaine Y Pietersen
Fokko J Bosker
Janine Doorduin
Minke E Jongsma
Folkert Postema
Joseph V Haas
Michael P Johnson
Tineke Koch
Tony Vladusich
Johan A den Boer
author_sort Charmaine Y Pietersen
collection DOAJ
description Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.
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spelling doaj.art-6b7498e791fb4f35b096ae79bbd8a2902022-12-22T03:15:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-01-01212e136010.1371/journal.pone.0001360An animal model of emotional blunting in schizophrenia.Charmaine Y PietersenFokko J BoskerJanine DoorduinMinke E JongsmaFolkert PostemaJoseph V HaasMichael P JohnsonTineke KochTony VladusichJohan A den BoerSchizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.http://europepmc.org/articles/PMC2137950?pdf=render
spellingShingle Charmaine Y Pietersen
Fokko J Bosker
Janine Doorduin
Minke E Jongsma
Folkert Postema
Joseph V Haas
Michael P Johnson
Tineke Koch
Tony Vladusich
Johan A den Boer
An animal model of emotional blunting in schizophrenia.
PLoS ONE
title An animal model of emotional blunting in schizophrenia.
title_full An animal model of emotional blunting in schizophrenia.
title_fullStr An animal model of emotional blunting in schizophrenia.
title_full_unstemmed An animal model of emotional blunting in schizophrenia.
title_short An animal model of emotional blunting in schizophrenia.
title_sort animal model of emotional blunting in schizophrenia
url http://europepmc.org/articles/PMC2137950?pdf=render
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