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Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

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dc.contributor.author Gracia Rubio, Irene, 1986-
dc.contributor.author Martinez-Laorden, Elena
dc.contributor.author Moscoso Castro, Maria, 1988-
dc.contributor.author Milanés, María Victoria
dc.contributor.author Laorden, María Luisa
dc.contributor.author Valverde Granados, Olga
dc.date.accessioned 2017-03-14T14:29:55Z
dc.date.available 2017-03-14T14:29:55Z
dc.date.issued 2016
dc.identifier.citation Gracia Rubio I, Martinez-Laorden E, Moscoso Castro M, Milanés MV, Laorden ML, Valverde Granados O. Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice. PLoS ONE. 2016; 11(12): e0167483. DOI: 10.1371/journal.pone.0167483
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/28227
dc.description.abstract Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.
dc.description.sponsorship This study was supported by UE MedBioinformatics project (Grant Agreement Number: 634143), MINECO (SAF2013-41761-R-FEDER and SAF2013-49076-P-FEDER), Spanish Ministry of Health (Retic-ISCIII-RD/12/0028/0024-FEDER and RETICS-ISCIII-RD 12/0028/003-FEDER and Plan Nacional sobre Drogas 2014/020), Generalitat de Catalunya (2014SGR34) and Fundación Séneca (15405/PI/10), Región de Murcia. IG-R was funded by FPI fellowship BES-2011-046655 associated to SAF2010-15793.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS ONE. 2016; 11(12): e0167483
dc.relation.ispartof PLoS ONE. 2016;11(12):e0167483
dc.rights © 2016 Gracia-Rubio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0167483
dc.subject.keyword Cocaine
dc.subject.keyword Mice
dc.subject.keyword Biological locomotion
dc.subject.keyword Animal behavior
dc.subject.keyword Body weight
dc.subject.keyword Analysis of variance
dc.subject.keyword Protein expression
dc.subject.keyword Dopaminergics
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-15793
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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