Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons

Autores
Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R.; Tagliaferro, Adriana; Brusco, Herminia Alicia; Bäckman, Cristina M.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine- induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories. © 2012 Cold Spring Harbor Laboratory Press.
Fil: Diaz-Ruiz, Oscar. National Institutes of Health; Estados Unidos
Fil: Zhang, YaJun. National Institutes of Health; Estados Unidos
Fil: Shan, Lufei. National Institutes of Health; Estados Unidos
Fil: Malik, Nasir. National Institutes of Health; Estados Unidos
Fil: Hoffman, Alexander F.. National Institutes of Health; Estados Unidos
Fil: Ladenheim, Bruce. National Institutes of Health; Estados Unidos
Fil: Cadet, Jean Lud. National Institutes of Health; Estados Unidos
Fil: Lupica, Carl R.. National Institutes of Health; Estados Unidos
Fil: Tagliaferro, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Bäckman, Cristina M.. National Institutes of Health; Estados Unidos
Materia
BETA CATENIN
METHANPHETAMINE
LEARNING
MEMORY
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:11336/67401
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67401
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neuronsDiaz-Ruiz, OscarZhang, YaJunShan, LufeiMalik, NasirHoffman, Alexander F.Ladenheim, BruceCadet, Jean LudLupica, Carl R.Tagliaferro, AdrianaBrusco, Herminia AliciaBäckman, Cristina M.BETA CATENINMETHANPHETAMINELEARNINGMEMORYhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine- induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories. © 2012 Cold Spring Harbor Laboratory Press.Fil: Diaz-Ruiz, Oscar. National Institutes of Health; Estados UnidosFil: Zhang, YaJun. National Institutes of Health; Estados UnidosFil: Shan, Lufei. National Institutes of Health; Estados UnidosFil: Malik, Nasir. National Institutes of Health; Estados UnidosFil: Hoffman, Alexander F.. National Institutes of Health; Estados UnidosFil: Ladenheim, Bruce. National Institutes of Health; Estados UnidosFil: Cadet, Jean Lud. National Institutes of Health; Estados UnidosFil: Lupica, Carl R.. National Institutes of Health; Estados UnidosFil: Tagliaferro, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; ArgentinaFil: Bäckman, Cristina M.. National Institutes of Health; Estados UnidosCold Spring Harbor Laboratory Press2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67401Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; et al.; Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons; Cold Spring Harbor Laboratory Press; Learning & Memory (Cold Spring Harbor, N.Y.); 19; 8; 8-2012; 341-3501072-0502CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://learnmem.cshlp.org/content/19/8/341info:eu-repo/semantics/altIdentifier/doi/10.1101/lm.026716.112info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:24:25Zoai:ri.conicet.gov.ar:11336/67401instacron: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:34982025-10-15 14:24:26.199CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
title Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
spellingShingle Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
Diaz-Ruiz, Oscar
BETA CATENIN
METHANPHETAMINE
LEARNING
MEMORY
title_short Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
title_full Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
title_fullStr Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
title_full_unstemmed Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
title_sort Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons
dc.creator.none.fl_str_mv Diaz-Ruiz, Oscar
Zhang, YaJun
Shan, Lufei
Malik, Nasir
Hoffman, Alexander F.
Ladenheim, Bruce
Cadet, Jean Lud
Lupica, Carl R.
Tagliaferro, Adriana
Brusco, Herminia Alicia
Bäckman, Cristina M.
author Diaz-Ruiz, Oscar
author_facet Diaz-Ruiz, Oscar
Zhang, YaJun
Shan, Lufei
Malik, Nasir
Hoffman, Alexander F.
Ladenheim, Bruce
Cadet, Jean Lud
Lupica, Carl R.
Tagliaferro, Adriana
Brusco, Herminia Alicia
Bäckman, Cristina M.
author_role author
author2 Zhang, YaJun
Shan, Lufei
Malik, Nasir
Hoffman, Alexander F.
Ladenheim, Bruce
Cadet, Jean Lud
Lupica, Carl R.
Tagliaferro, Adriana
Brusco, Herminia Alicia
Bäckman, Cristina M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BETA CATENIN
METHANPHETAMINE
LEARNING
MEMORY
topic BETA CATENIN
METHANPHETAMINE
LEARNING
MEMORY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine- induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories. © 2012 Cold Spring Harbor Laboratory Press.
Fil: Diaz-Ruiz, Oscar. National Institutes of Health; Estados Unidos
Fil: Zhang, YaJun. National Institutes of Health; Estados Unidos
Fil: Shan, Lufei. National Institutes of Health; Estados Unidos
Fil: Malik, Nasir. National Institutes of Health; Estados Unidos
Fil: Hoffman, Alexander F.. National Institutes of Health; Estados Unidos
Fil: Ladenheim, Bruce. National Institutes of Health; Estados Unidos
Fil: Cadet, Jean Lud. National Institutes of Health; Estados Unidos
Fil: Lupica, Carl R.. National Institutes of Health; Estados Unidos
Fil: Tagliaferro, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Bäckman, Cristina M.. National Institutes of Health; Estados Unidos
description In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine- induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories. © 2012 Cold Spring Harbor Laboratory Press.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
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/11336/67401
Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; et al.; Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons; Cold Spring Harbor Laboratory Press; Learning & Memory (Cold Spring Harbor, N.Y.); 19; 8; 8-2012; 341-350
1072-0502
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67401
identifier_str_mv Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; et al.; Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons; Cold Spring Harbor Laboratory Press; Learning & Memory (Cold Spring Harbor, N.Y.); 19; 8; 8-2012; 341-350
1072-0502
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://learnmem.cshlp.org/content/19/8/341
info:eu-repo/semantics/altIdentifier/doi/10.1101/lm.026716.112
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
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory 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 13.22299

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