Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory

Autores
Castillo Díaz, Fernando; Hernández, Micaela Anahí; Capellá, Tomás; Medina, Jorge Horacio
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation. Inhibition of VTA D1R results in increased activation of VTA ERK1/2 and in prolonging memory storage of cocaine-place association in an ERK-dependent manner. Moreover, intra-VTA infusion of a specific D1 agonist induces forgetting of cocaine-associated consolidated memory. In contrast, D1R in the NAc shell, medial prefrontal cortex, or amygdala appear not to participate in the maintenance of cocaine-associated memory. Our present results suggest that at the moment of learning D1R-mediated neurotransmission in the VTA actively participates in at least two processes affecting the fate of appetitive memory: its consolidation involving NAc shell DA neurotransmission and its forgetting via DA activation of the hippocampus.
Fil: Castillo Díaz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hernández, Micaela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Capellá, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Medina, Jorge Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia
COCAINE
DOPAMINE
FORGETTING
MEMORY
VTA
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:11336/132275
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/132275
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated MemoryCastillo Díaz, FernandoHernández, Micaela AnahíCapellá, TomásMedina, Jorge HoracioCOCAINEDOPAMINEFORGETTINGMEMORYVTAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation. Inhibition of VTA D1R results in increased activation of VTA ERK1/2 and in prolonging memory storage of cocaine-place association in an ERK-dependent manner. Moreover, intra-VTA infusion of a specific D1 agonist induces forgetting of cocaine-associated consolidated memory. In contrast, D1R in the NAc shell, medial prefrontal cortex, or amygdala appear not to participate in the maintenance of cocaine-associated memory. Our present results suggest that at the moment of learning D1R-mediated neurotransmission in the VTA actively participates in at least two processes affecting the fate of appetitive memory: its consolidation involving NAc shell DA neurotransmission and its forgetting via DA activation of the hippocampus.Fil: Castillo Díaz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Hernández, Micaela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Capellá, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Medina, Jorge Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaHumana Press2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/132275Castillo Díaz, Fernando; Hernández, Micaela Anahí; Capellá, Tomás; Medina, Jorge Horacio; Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory; Humana Press; Molecular Neurobiology; 56; 9; 9-2019; 6206-62170893-7648CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-019-1516-3info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s12035-019-1516-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:13:38Zoai:ri.conicet.gov.ar:11336/132275instacron: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 10:13:38.953CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
title Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
spellingShingle Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
Castillo Díaz, Fernando
COCAINE
DOPAMINE
FORGETTING
MEMORY
VTA
title_short Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
title_full Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
title_fullStr Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
title_full_unstemmed Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
title_sort Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
dc.creator.none.fl_str_mv Castillo Díaz, Fernando
Hernández, Micaela Anahí
Capellá, Tomás
Medina, Jorge Horacio
author Castillo Díaz, Fernando
author_facet Castillo Díaz, Fernando
Hernández, Micaela Anahí
Capellá, Tomás
Medina, Jorge Horacio
author_role author
author2 Hernández, Micaela Anahí
Capellá, Tomás
Medina, Jorge Horacio
author2_role author
author
author
dc.subject.none.fl_str_mv COCAINE
DOPAMINE
FORGETTING
MEMORY
VTA
topic COCAINE
DOPAMINE
FORGETTING
MEMORY
VTA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation. Inhibition of VTA D1R results in increased activation of VTA ERK1/2 and in prolonging memory storage of cocaine-place association in an ERK-dependent manner. Moreover, intra-VTA infusion of a specific D1 agonist induces forgetting of cocaine-associated consolidated memory. In contrast, D1R in the NAc shell, medial prefrontal cortex, or amygdala appear not to participate in the maintenance of cocaine-associated memory. Our present results suggest that at the moment of learning D1R-mediated neurotransmission in the VTA actively participates in at least two processes affecting the fate of appetitive memory: its consolidation involving NAc shell DA neurotransmission and its forgetting via DA activation of the hippocampus.
Fil: Castillo Díaz, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Hernández, Micaela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Capellá, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Medina, Jorge Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation. Inhibition of VTA D1R results in increased activation of VTA ERK1/2 and in prolonging memory storage of cocaine-place association in an ERK-dependent manner. Moreover, intra-VTA infusion of a specific D1 agonist induces forgetting of cocaine-associated consolidated memory. In contrast, D1R in the NAc shell, medial prefrontal cortex, or amygdala appear not to participate in the maintenance of cocaine-associated memory. Our present results suggest that at the moment of learning D1R-mediated neurotransmission in the VTA actively participates in at least two processes affecting the fate of appetitive memory: its consolidation involving NAc shell DA neurotransmission and its forgetting via DA activation of the hippocampus.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
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/11336/132275
Castillo Díaz, Fernando; Hernández, Micaela Anahí; Capellá, Tomás; Medina, Jorge Horacio; Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory; Humana Press; Molecular Neurobiology; 56; 9; 9-2019; 6206-6217
0893-7648
CONICET Digital
CONICET
url http://hdl.handle.net/11336/132275
identifier_str_mv Castillo Díaz, Fernando; Hernández, Micaela Anahí; Capellá, Tomás; Medina, Jorge Horacio; Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory; Humana Press; Molecular Neurobiology; 56; 9; 9-2019; 6206-6217
0893-7648
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-019-1516-3
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s12035-019-1516-3
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 Humana Press
publisher.none.fl_str_mv Humana 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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