Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action

Autores
Celada, Pau; Lladó Pelfort, L.; Santana, N.; Kargieman, Lucila; Troyano Rodriguez, Eva; Riga, M. S.; Artigas, Francesc
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.
Fil: Celada, Pau. Consejo Superior de Investigaciones Científicas; España. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España
Fil: Lladó Pelfort, L.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Santana, N.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Kargieman, Lucila. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Troyano Rodriguez, Eva. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Riga, M. S.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Artigas, Francesc. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España
Materia
5-Ht Receptors
Antipsychotic Drugs
Nmda Receptors
Prefrontal Cortex
Thalamus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25424
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug actionCelada, PauLladó Pelfort, L.Santana, N.Kargieman, LucilaTroyano Rodriguez, EvaRiga, M. S.Artigas, Francesc5-Ht ReceptorsAntipsychotic DrugsNmda ReceptorsPrefrontal CortexThalamushttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.Fil: Celada, Pau. Consejo Superior de Investigaciones Científicas; España. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; EspañaFil: Lladó Pelfort, L.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Santana, N.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Kargieman, Lucila. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Troyano Rodriguez, Eva. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Riga, M. S.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Artigas, Francesc. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; EspañaCambridge University Press2013-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25424Celada, Pau; Lladó Pelfort, L.; Santana, N.; Kargieman, Lucila; Troyano Rodriguez, Eva; et al.; Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action; Cambridge University Press; International Journal Of Neuropsychopharmacology; 16; 10; 11-2013; 2145-21631461-1457CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1017/S1461145713000643info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145713000643info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:50Zoai:ri.conicet.gov.ar:11336/25424instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:37:50.374CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
title Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
spellingShingle Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
Celada, Pau
5-Ht Receptors
Antipsychotic Drugs
Nmda Receptors
Prefrontal Cortex
Thalamus
title_short Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
title_full Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
title_fullStr Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
title_full_unstemmed Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
title_sort Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action
dc.creator.none.fl_str_mv Celada, Pau
Lladó Pelfort, L.
Santana, N.
Kargieman, Lucila
Troyano Rodriguez, Eva
Riga, M. S.
Artigas, Francesc
author Celada, Pau
author_facet Celada, Pau
Lladó Pelfort, L.
Santana, N.
Kargieman, Lucila
Troyano Rodriguez, Eva
Riga, M. S.
Artigas, Francesc
author_role author
author2 Lladó Pelfort, L.
Santana, N.
Kargieman, Lucila
Troyano Rodriguez, Eva
Riga, M. S.
Artigas, Francesc
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv 5-Ht Receptors
Antipsychotic Drugs
Nmda Receptors
Prefrontal Cortex
Thalamus
topic 5-Ht Receptors
Antipsychotic Drugs
Nmda Receptors
Prefrontal Cortex
Thalamus
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.
Fil: Celada, Pau. Consejo Superior de Investigaciones Científicas; España. Centro de Investigación Biomédica en Red de Salud Mental; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España
Fil: Lladó Pelfort, L.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Santana, N.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Kargieman, Lucila. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Troyano Rodriguez, Eva. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Riga, M. S.. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España. Consejo Superior de Investigaciones Científicas; España
Fil: Artigas, Francesc. Consejo Superior de Investigaciones Científicas; España. Institut d'Investigacions Biomèdiques de Barcelona. Department of Neurochemistry and Neuropharmacology; España
description Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.
publishDate 2013
dc.date.none.fl_str_mv 2013-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25424
Celada, Pau; Lladó Pelfort, L.; Santana, N.; Kargieman, Lucila; Troyano Rodriguez, Eva; et al.; Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action; Cambridge University Press; International Journal Of Neuropsychopharmacology; 16; 10; 11-2013; 2145-2163
1461-1457
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25424
identifier_str_mv Celada, Pau; Lladó Pelfort, L.; Santana, N.; Kargieman, Lucila; Troyano Rodriguez, Eva; et al.; Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action; Cambridge University Press; International Journal Of Neuropsychopharmacology; 16; 10; 11-2013; 2145-2163
1461-1457
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1017/S1461145713000643
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145713000643
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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