Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors

The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4 -/- ) and their wild-type (WT) l...

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Autores: Nemirovsky, Sergio Ivan, Avale, Maria Elena, Brunner, Daniela, Rubinstein, Marcelo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/79491
Acceso en línea:http://hdl.handle.net/11336/79491
Access Level:acceso abierto
Palabra clave:6-Hydroxydopamine
Adhd
D4r Knockout Mouse
Dopamine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79491
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
title Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
spellingShingle Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
Nemirovsky, Sergio Ivan
6-Hydroxydopamine
Adhd
D4r Knockout Mouse
Dopamine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
title_full Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
title_fullStr Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
title_full_unstemmed Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
title_sort Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors
dc.creator.none.fl_str_mv Nemirovsky, Sergio Ivan
Avale, Maria Elena
Brunner, Daniela
Rubinstein, Marcelo
author Nemirovsky, Sergio Ivan
author_facet Nemirovsky, Sergio Ivan
Avale, Maria Elena
Brunner, Daniela
Rubinstein, Marcelo
author_role author
author2 Avale, Maria Elena
Brunner, Daniela
Rubinstein, Marcelo
author2_role author
author
author
dc.subject.none.fl_str_mv 6-Hydroxydopamine
Adhd
D4r Knockout Mouse
Dopamine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic 6-Hydroxydopamine
Adhd
D4r Knockout Mouse
Dopamine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4 -/- ) and their wild-type (WT) littermates, neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant learning paradigms. A continuous reinforcement task, in which one food-pellet was delivered after every lever press, showed that 6-OHDA-treated mice (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than normodopaminergic WT mice. In contrast, Drd4 -/- mice displayed increased lever pressing rates, regardless of their dopamine content. In another study, mice were trained to solve an operant two-choice task in which a first showing lever was coupled to the delivery of one food pellet only after a second lever emerged. Interval between presentation of both levers was initially 12 s and progressively shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs was not detrimental in this task. Moreover, hypodopaminergic Drd4 -/- mice were as efficient as their normodopaminergic Drd4 -/- siblings in selecting the reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
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/11336/79491
Nemirovsky, Sergio Ivan; Avale, Maria Elena; Brunner, Daniela; Rubinstein, Marcelo; Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors; Wiley-liss, Div John Wiley & Sons Inc; Synapse; 63; 11; 11-2009; 991-997
0887-4476
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79491
identifier_str_mv Nemirovsky, Sergio Ivan; Avale, Maria Elena; Brunner, Daniela; Rubinstein, Marcelo; Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors; Wiley-liss, Div John Wiley & Sons Inc; Synapse; 63; 11; 11-2009; 991-997
0887-4476
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/19598175
info:eu-repo/semantics/altIdentifier/doi/10.1002/syn.20680
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/syn.20680
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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spelling Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptorsNemirovsky, Sergio IvanAvale, Maria ElenaBrunner, DanielaRubinstein, Marcelo6-HydroxydopamineAdhdD4r Knockout MouseDopaminehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4 -/- ) and their wild-type (WT) littermates, neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant learning paradigms. A continuous reinforcement task, in which one food-pellet was delivered after every lever press, showed that 6-OHDA-treated mice (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than normodopaminergic WT mice. In contrast, Drd4 -/- mice displayed increased lever pressing rates, regardless of their dopamine content. In another study, mice were trained to solve an operant two-choice task in which a first showing lever was coupled to the delivery of one food pellet only after a second lever emerged. Interval between presentation of both levers was initially 12 s and progressively shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs was not detrimental in this task. Moreover, hypodopaminergic Drd4 -/- mice were as efficient as their normodopaminergic Drd4 -/- siblings in selecting the reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs.Fil: Nemirovsky, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Brunner, Daniela. PsychoGenics; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaWiley-liss, Div John Wiley & Sons Inc2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79491Nemirovsky, Sergio Ivan; Avale, Maria Elena; Brunner, Daniela; Rubinstein, Marcelo; Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors; Wiley-liss, Div John Wiley & Sons Inc; Synapse; 63; 11; 11-2009; 991-9970887-4476CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/19598175info:eu-repo/semantics/altIdentifier/doi/10.1002/syn.20680info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/syn.20680info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:02:49Zoai:ri.conicet.gov.ar:11336/79491instacron: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:34982024-05-08 14:02:49.899CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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