Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors

Autores
Bello Gay, Estefania Pilar; Mateo, Yolanda; Gelman, Diego Matias; Noain, Daniela Maria Clara; Shin, Jung H.; Low, Malcolm J.; Alvarez, Veronica A.; Lovinger, David M.; Rubinstein, Marcelo
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Mateo, Yolanda. National Institutes of Health; Estados Unidos
Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Shin, Jung H.. National Institutes of Health; Estados Unidos
Fil: Low, Malcolm J.. University of Michigan Medical School; Estados Unidos
Fil: Alvarez, Veronica A.. National Institutes of Health; Estados Unidos
Fil: Lovinger, David M.. National Institutes of Health; Estados Unidos
Fil: 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; Argentina
Materia
Dopamina
Supersensibilidad
Cocaina
Cre
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79453
Acceder
id CONICETDig_f3de965033a633fa2c58876466d35626
oai_identifier_str oai:ri.conicet.gov.ar:11336/79453
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptorsBello Gay, Estefania PilarMateo, YolandaGelman, Diego MatiasNoain, Daniela Maria ClaraShin, Jung H.Low, Malcolm J.Alvarez, Veronica A.Lovinger, David M.Rubinstein, MarceloDopaminaSupersensibilidadCocainaCrehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Mateo, Yolanda. National Institutes of Health; Estados UnidosFil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Shin, Jung H.. National Institutes of Health; Estados UnidosFil: Low, Malcolm J.. University of Michigan Medical School; Estados UnidosFil: Alvarez, Veronica A.. National Institutes of Health; Estados UnidosFil: Lovinger, David M.. National Institutes of Health; 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; ArgentinaNature Publishing Group2011-08info: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/11336/79453Bello Gay, Estefania Pilar; Mateo, Yolanda; Gelman, Diego Matias; Noain, Daniela Maria Clara; Shin, Jung H.; et al.; Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors; Nature Publishing Group; Nature Neuroscience.; 14; 8; 8-2011; 1033-10381097-6256CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/nn.2862info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.2862info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:05Zoai:ri.conicet.gov.ar:11336/79453instacron: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 09:58:05.543CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
spellingShingle Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
Bello Gay, Estefania Pilar
Dopamina
Supersensibilidad
Cocaina
Cre
title_short Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_full Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_fullStr Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_full_unstemmed Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_sort Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
dc.creator.none.fl_str_mv Bello Gay, Estefania Pilar
Mateo, Yolanda
Gelman, Diego Matias
Noain, Daniela Maria Clara
Shin, Jung H.
Low, Malcolm J.
Alvarez, Veronica A.
Lovinger, David M.
Rubinstein, Marcelo
author Bello Gay, Estefania Pilar
author_facet Bello Gay, Estefania Pilar
Mateo, Yolanda
Gelman, Diego Matias
Noain, Daniela Maria Clara
Shin, Jung H.
Low, Malcolm J.
Alvarez, Veronica A.
Lovinger, David M.
Rubinstein, Marcelo
author_role author
author2 Mateo, Yolanda
Gelman, Diego Matias
Noain, Daniela Maria Clara
Shin, Jung H.
Low, Malcolm J.
Alvarez, Veronica A.
Lovinger, David M.
Rubinstein, Marcelo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dopamina
Supersensibilidad
Cocaina
Cre
topic Dopamina
Supersensibilidad
Cocaina
Cre
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Mateo, Yolanda. National Institutes of Health; Estados Unidos
Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Shin, Jung H.. National Institutes of Health; Estados Unidos
Fil: Low, Malcolm J.. University of Michigan Medical School; Estados Unidos
Fil: Alvarez, Veronica A.. National Institutes of Health; Estados Unidos
Fil: Lovinger, David M.. National Institutes of Health; Estados Unidos
Fil: 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; Argentina
description Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
publishDate 2011
dc.date.none.fl_str_mv 2011-08
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/11336/79453
Bello Gay, Estefania Pilar; Mateo, Yolanda; Gelman, Diego Matias; Noain, Daniela Maria Clara; Shin, Jung H.; et al.; Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors; Nature Publishing Group; Nature Neuroscience.; 14; 8; 8-2011; 1033-1038
1097-6256
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79453
identifier_str_mv Bello Gay, Estefania Pilar; Mateo, Yolanda; Gelman, Diego Matias; Noain, Daniela Maria Clara; Shin, Jung H.; et al.; Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors; Nature Publishing Group; Nature Neuroscience.; 14; 8; 8-2011; 1033-1038
1097-6256
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/nn.2862
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.2862
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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