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

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  • dc.contributor.author Cabana-Domínguez, Judit
  • dc.contributor.author Martín-García, Elena
  • dc.contributor.author Gallego-Roman, Ana
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.contributor.author Fernández-Castillo, Noèlia
  • dc.contributor.author Comand, Bru
  • dc.date.accessioned 2022-03-18T10:53:26Z
  • dc.date.available 2022-03-18T10:53:26Z
  • dc.date.issued 2021
  • dc.description.abstract 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.
  • dc.description.sponsorship 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 projects
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Cabana-Domínguez J, Martín-García E, Gallego-Roman A, Maldonado R, Fernández-Castillo N, Comand B.Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice. Transl Psychiatry. 2021 Oct 11;11(1):521. DOI: 10.1038/s41398-021-01396-6
  • dc.identifier.doi http://dx.doi.org/10.1038/s41398-021-01396-6
  • dc.identifier.issn 2158-3188
  • dc.identifier.uri http://hdl.handle.net/10230/52721
  • dc.language.iso eng
  • dc.publisher Springer Nature
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667302
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/643051
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68341-R
  • dc.rights © 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 made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Cocaïnomania
  • dc.subject.other Genètica
  • dc.title Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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