Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice

Cocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells a...

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Autores: Cabana-Domínguez, Judit, Martín García, Elena, 1975-, Gallego-Roman, Ana, Maldonado, Rafael, 1961-, Fernández-Castillo, Noèlia, Comand, Bru
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/52721
Acceso en línea:http://hdl.handle.net/10230/52721
http://dx.doi.org/10.1038/s41398-021-01396-6
Access Level:acceso abierto
Palabra clave:Cocaïnomania
Genètica
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spelling Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- miceCabana-Domínguez, JuditMartín García, Elena, 1975-Gallego-Roman, AnaMaldonado, Rafael, 1961-Fernández-Castillo, NoèliaComand, BruCocaïnomaniaGenèticaCocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of the PLCB1 gene to cocaine addictive properties using Plcb1+/- mice. First, we performed a general phenotypic characterization and found that Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Subsequently, mice were trained for operant conditioning, self-administered cocaine for 10 days, and were tested for cocaine motivation. After extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine-seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.This work was supported by the Spanish ‘Ministerio de Economía y Competitividad-MINECO’ (#SAF2017-84060-RAEI/FEDER-UE), the Spanish ‘Instituto de Salud Carlos III, RETICS-RTA’ (#RD12/0028/0023), the ‘Generalitat de Catalunya, AGAUR’ (#2017 SGR-669), ‘ICREA-Acadèmia’ (#2015) and the Spanish ‘Ministerio de Sanidad, Servicios Sociales e Igualdad/Plan Nacional Sobre Drogas’ (#PNSD-2017I068) to RM, ‘Fundació La Marató-TV3’ (#2016/20-30) and ‘Plan Nacional Sobre Drogas of the Spanish Ministry of Health’ (#PNSD-2019I006) to EMG, Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (#RTI2018-100968-B-100), Spanish ‘Ministerio de Economía y Competitividad’ (#SAF2015-68341-R), ‘AGAURGeneralitat de Catalunya’ (#2017-SGR-738) and Spanish ‘Ministerio de Sanidad, Servicios Sociales e Igualdad/Plan Nacional Sobre Drogas’ (#PNSD-2017I050) to BC and (#PNSD-2020I042) to NFC. The research leading to these results has also received funding from the European Union H2020 Program [H2020/2014-2020] under grant agreements n° 667302 (CoCA), 643051 (MiND) and 728018 (Eat2beNICE). JCD was supported by the H2020 CoCA and Eat2beNICE projectsSpringer Nature202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/52721http://dx.doi.org/10.1038/s41398-021-01396-6reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésinfo:eu-repo/grantAgreement/EC/H2020/667302info:eu-repo/grantAgreement/EC/H2020/643051info:eu-repo/grantAgreement/EC/H2020/728018info:eu-repo/grantAgreement/ES/1PE/SAF2015-68341-R© Juidit Cabana-Domínguez et al. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madehttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/527212026-06-12T07:21:37Z
dc.title.none.fl_str_mv Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
title Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
spellingShingle Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
Cabana-Domínguez, Judit
Cocaïnomania
Genètica
title_short Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
title_full Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
title_fullStr Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
title_full_unstemmed Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
title_sort Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
dc.creator.none.fl_str_mv Cabana-Domínguez, Judit
Martín García, Elena, 1975-
Gallego-Roman, Ana
Maldonado, Rafael, 1961-
Fernández-Castillo, Noèlia
Comand, Bru
author Cabana-Domínguez, Judit
author_facet Cabana-Domínguez, Judit
Martín García, Elena, 1975-
Gallego-Roman, Ana
Maldonado, Rafael, 1961-
Fernández-Castillo, Noèlia
Comand, Bru
author_role author
author2 Martín García, Elena, 1975-
Gallego-Roman, Ana
Maldonado, Rafael, 1961-
Fernández-Castillo, Noèlia
Comand, Bru
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cocaïnomania
Genètica
topic Cocaïnomania
Genètica
description Cocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of the PLCB1 gene to cocaine addictive properties using Plcb1+/- mice. First, we performed a general phenotypic characterization and found that Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Subsequently, mice were trained for operant conditioning, self-administered cocaine for 10 days, and were tested for cocaine motivation. After extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine-seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/52721
http://dx.doi.org/10.1038/s41398-021-01396-6
url http://hdl.handle.net/10230/52721
http://dx.doi.org/10.1038/s41398-021-01396-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/667302
info:eu-repo/grantAgreement/EC/H2020/643051
info:eu-repo/grantAgreement/EC/H2020/728018
info:eu-repo/grantAgreement/ES/1PE/SAF2015-68341-R
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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