Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors

Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1...

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Autores: Bortolozzi Biasoni, Analía, Masana Nadal, Mercè, Díaz Mataix, Llorenç, Cortés, Roser, Scorza, María Cecilia, Gingrich, Jay A, Toth, Miklos, Artigas Pérez, Francesc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/164959
Acceso en línea:https://hdl.handle.net/2445/164959
Access Level:acceso abierto
Palabra clave:Antipsicòtics
Dopamina
Escorça frontal
Receptors de serotonina
Antipsychotic drugs
Dopamine
Prefrontal cortex
Serotonin receptors
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spelling Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) ReceptorsBortolozzi Biasoni, AnalíaMasana Nadal, MercèDíaz Mataix, LlorençCortés, RoserScorza, María CeciliaGingrich, Jay AToth, MiklosArtigas Pérez, FrancescAntipsicòticsDopaminaEscorça frontalReceptors de serotoninaAntipsychotic drugsDopaminePrefrontal cortexSerotonin receptorsAtypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1A)Rs and 5-HT(2A) receptors (5-HT(2A)Rs) in the PFC, this effect might result from the imbalance of 5-HT(1A)R and 5-HT(2A)R activation after blockade of these receptors by APDs, for which they show high affinity. Here we tested this hypothesis by examining the dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by using in-vivo microdialysis in wild-type (WT) and 5-HT(1A)R and 5-HT(2A)R knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered by reverse dialysis induced a dose-dependent increase in mPFC DA output equally in WT and 5-HT(2A)R KO mice whereas the DA increase was absent in 5-HT(1A)R KO mice. To examine the relative contribution of both receptors to the clozapine-induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs) in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5-HT(1A)Rs or 5-HT(2A)/2CRs in the mPFC were selectively protected with the respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while preserving ∼70% of 5-HT(2A)/(2C)Rs prevented the clozapine-induced DA rise in mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5-HT(1A)Rs were protected (∼50% of control rats). These results indicate that (1) 5-HT(1A)Rs are necessary for the APDs-induced elevation in cortical DA transmission, and (2) this effect does not require 5-HT(2A)R blockade by APDs.Oxford University Press2020202020102020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/164959Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1017/S146114571000009XInternational Journal of Neuropsychopharmacology, 2010, vol. 13, num. 10, p. 1299-1314https://doi.org/10.1017/S146114571000009X(c) CINP (Collegium Internationale Neuro-Psychopharmacologicum) , 2010info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1649592026-05-29T05:05:01Z
dc.title.none.fl_str_mv Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
title Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
spellingShingle Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
Bortolozzi Biasoni, Analía
Antipsicòtics
Dopamina
Escorça frontal
Receptors de serotonina
Antipsychotic drugs
Dopamine
Prefrontal cortex
Serotonin receptors
title_short Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
title_full Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
title_fullStr Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
title_full_unstemmed Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
title_sort Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors
dc.creator.none.fl_str_mv Bortolozzi Biasoni, Analía
Masana Nadal, Mercè
Díaz Mataix, Llorenç
Cortés, Roser
Scorza, María Cecilia
Gingrich, Jay A
Toth, Miklos
Artigas Pérez, Francesc
author Bortolozzi Biasoni, Analía
author_facet Bortolozzi Biasoni, Analía
Masana Nadal, Mercè
Díaz Mataix, Llorenç
Cortés, Roser
Scorza, María Cecilia
Gingrich, Jay A
Toth, Miklos
Artigas Pérez, Francesc
author_role author
author2 Masana Nadal, Mercè
Díaz Mataix, Llorenç
Cortés, Roser
Scorza, María Cecilia
Gingrich, Jay A
Toth, Miklos
Artigas Pérez, Francesc
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antipsicòtics
Dopamina
Escorça frontal
Receptors de serotonina
Antipsychotic drugs
Dopamine
Prefrontal cortex
Serotonin receptors
topic Antipsicòtics
Dopamina
Escorça frontal
Receptors de serotonina
Antipsychotic drugs
Dopamine
Prefrontal cortex
Serotonin receptors
description Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1A)Rs and 5-HT(2A) receptors (5-HT(2A)Rs) in the PFC, this effect might result from the imbalance of 5-HT(1A)R and 5-HT(2A)R activation after blockade of these receptors by APDs, for which they show high affinity. Here we tested this hypothesis by examining the dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by using in-vivo microdialysis in wild-type (WT) and 5-HT(1A)R and 5-HT(2A)R knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered by reverse dialysis induced a dose-dependent increase in mPFC DA output equally in WT and 5-HT(2A)R KO mice whereas the DA increase was absent in 5-HT(1A)R KO mice. To examine the relative contribution of both receptors to the clozapine-induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs) in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5-HT(1A)Rs or 5-HT(2A)/2CRs in the mPFC were selectively protected with the respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while preserving ∼70% of 5-HT(2A)/(2C)Rs prevented the clozapine-induced DA rise in mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5-HT(1A)Rs were protected (∼50% of control rats). These results indicate that (1) 5-HT(1A)Rs are necessary for the APDs-induced elevation in cortical DA transmission, and (2) this effect does not require 5-HT(2A)R blockade by APDs.
publishDate 2010
dc.date.none.fl_str_mv 2010
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/164959
url https://hdl.handle.net/2445/164959
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1017/S146114571000009X
International Journal of Neuropsychopharmacology, 2010, vol. 13, num. 10, p. 1299-1314
https://doi.org/10.1017/S146114571000009X
dc.rights.none.fl_str_mv (c) CINP (Collegium Internationale Neuro-Psychopharmacologicum) , 2010
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) CINP (Collegium Internationale Neuro-Psychopharmacologicum) , 2010
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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