A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Autores
Bocarsly, Miriam E.; da Silva e Silva, Daniel; Kolb, Vanessa; Luderman, Kathryn D.; Shashikiran, Sannidhi; Rubinstein, Marcelo; Sibley, David R.; Dobbs, Lauren K.; Álvarez, Verónica Alicia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking
Fil: Bocarsly, Miriam E.. National Institutes of Health; Estados Unidos
Fil: da Silva e Silva, Daniel. National Institutes of Health; Estados Unidos
Fil: Kolb, Vanessa. National Institutes of Health; Estados Unidos
Fil: Luderman, Kathryn D.. National Institutes of Health; Estados Unidos
Fil: Shashikiran, Sannidhi. 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
Fil: Sibley, David R.. National Institutes of Health; Estados Unidos
Fil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados Unidos
Fil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unidos
Materia
ALCOHOL USE DISORDERS
DOPAMINE D1 RECEPTORS
DORSAL MEDIAL STRIATUM
ETHANOL
ETHANOL SELF-ADMINISTRATION
LOSS OF RIGHTING REFLEX
SEDATION
STRIATUM
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:11336/105330
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/105330
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 ReceptorsBocarsly, Miriam E.da Silva e Silva, DanielKolb, VanessaLuderman, Kathryn D.Shashikiran, SannidhiRubinstein, MarceloSibley, David R.Dobbs, Lauren K.Álvarez, Verónica AliciaALCOHOL USE DISORDERSDOPAMINE D1 RECEPTORSDORSAL MEDIAL STRIATUMETHANOLETHANOL SELF-ADMINISTRATIONLOSS OF RIGHTING REFLEXSEDATIONSTRIATUMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinkingFil: Bocarsly, Miriam E.. National Institutes of Health; Estados UnidosFil: da Silva e Silva, Daniel. National Institutes of Health; Estados UnidosFil: Kolb, Vanessa. National Institutes of Health; Estados UnidosFil: Luderman, Kathryn D.. National Institutes of Health; Estados UnidosFil: Shashikiran, Sannidhi. 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; ArgentinaFil: Sibley, David R.. National Institutes of Health; Estados UnidosFil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados UnidosFil: Álvarez, Verónica Alicia. National Institutes of Health; Estados UnidosElsevier2019-10-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105330Bocarsly, Miriam E.; da Silva e Silva, Daniel; Kolb, Vanessa; Luderman, Kathryn D.; Shashikiran, Sannidhi; et al.; A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors; Elsevier; Cell Reports; 29; 5; 29-10-2019; 1147-11632639-18562211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2019.09.059info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880649/info:eu-repo/semantics/altIdentifier/url/https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31256-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719312562%3Fshowall%3Dtrueinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:02:25Zoai:ri.conicet.gov.ar:11336/105330instacron: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:34982025-10-22 12:02:26.001CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
title A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
spellingShingle A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
Bocarsly, Miriam E.
ALCOHOL USE DISORDERS
DOPAMINE D1 RECEPTORS
DORSAL MEDIAL STRIATUM
ETHANOL
ETHANOL SELF-ADMINISTRATION
LOSS OF RIGHTING REFLEX
SEDATION
STRIATUM
title_short A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
title_full A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
title_fullStr A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
title_full_unstemmed A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
title_sort A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors
dc.creator.none.fl_str_mv Bocarsly, Miriam E.
da Silva e Silva, Daniel
Kolb, Vanessa
Luderman, Kathryn D.
Shashikiran, Sannidhi
Rubinstein, Marcelo
Sibley, David R.
Dobbs, Lauren K.
Álvarez, Verónica Alicia
author Bocarsly, Miriam E.
author_facet Bocarsly, Miriam E.
da Silva e Silva, Daniel
Kolb, Vanessa
Luderman, Kathryn D.
Shashikiran, Sannidhi
Rubinstein, Marcelo
Sibley, David R.
Dobbs, Lauren K.
Álvarez, Verónica Alicia
author_role author
author2 da Silva e Silva, Daniel
Kolb, Vanessa
Luderman, Kathryn D.
Shashikiran, Sannidhi
Rubinstein, Marcelo
Sibley, David R.
Dobbs, Lauren K.
Álvarez, Verónica Alicia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALCOHOL USE DISORDERS
DOPAMINE D1 RECEPTORS
DORSAL MEDIAL STRIATUM
ETHANOL
ETHANOL SELF-ADMINISTRATION
LOSS OF RIGHTING REFLEX
SEDATION
STRIATUM
topic ALCOHOL USE DISORDERS
DOPAMINE D1 RECEPTORS
DORSAL MEDIAL STRIATUM
ETHANOL
ETHANOL SELF-ADMINISTRATION
LOSS OF RIGHTING REFLEX
SEDATION
STRIATUM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking
Fil: Bocarsly, Miriam E.. National Institutes of Health; Estados Unidos
Fil: da Silva e Silva, Daniel. National Institutes of Health; Estados Unidos
Fil: Kolb, Vanessa. National Institutes of Health; Estados Unidos
Fil: Luderman, Kathryn D.. National Institutes of Health; Estados Unidos
Fil: Shashikiran, Sannidhi. 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
Fil: Sibley, David R.. National Institutes of Health; Estados Unidos
Fil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados Unidos
Fil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unidos
description Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking
publishDate 2019
dc.date.none.fl_str_mv 2019-10-29
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/11336/105330
Bocarsly, Miriam E.; da Silva e Silva, Daniel; Kolb, Vanessa; Luderman, Kathryn D.; Shashikiran, Sannidhi; et al.; A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors; Elsevier; Cell Reports; 29; 5; 29-10-2019; 1147-1163
2639-1856
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/105330
identifier_str_mv Bocarsly, Miriam E.; da Silva e Silva, Daniel; Kolb, Vanessa; Luderman, Kathryn D.; Shashikiran, Sannidhi; et al.; A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors; Elsevier; Cell Reports; 29; 5; 29-10-2019; 1147-1163
2639-1856
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2019.09.059
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880649/
info:eu-repo/semantics/altIdentifier/url/https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31256-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719312562%3Fshowall%3Dtrue
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 Elsevier
publisher.none.fl_str_mv Elsevier
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 12.982451

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