Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier

Rodríguez-Arias, Marta; Montagud-Romero, Sandra; Rubio-Araiz, Ana; Aguilar Morón, María Asunción; Martín García, Elena, 1975-; Cabrera Ortega, Roberto; Maldonado, Rafael, 1961-; Porcu, Francesca; Colado, María Isabel; Miñarro, José

Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier

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dc.contributor.author Rodríguez-Arias, Martaca
dc.contributor.author Montagud-Romero, Sandraca
dc.contributor.author Rubio-Araiz, Anaca
dc.contributor.author Aguilar Morón, María Asunciónca
dc.contributor.author Martín García, Elena, 1975-ca
dc.contributor.author Cabrera Ortega, Robertoca
dc.contributor.author Maldonado, Rafael, 1961-ca
dc.contributor.author Porcu, Francescaca
dc.contributor.author Colado, María Isabelca
dc.contributor.author Miñarro, Joséca
dc.date.accessioned 2017-05-03T09:58:42Z
dc.date.available 2017-05-03T09:58:42Z
dc.date.issued 2017
dc.description.abstract Social stress in adulthood enhances cocaine self-administration, an effect that has been related with an increase in extracellular signal-regulated kinase and p38α mitogen-activated protein kinase phosphorylation. A detrimental effect of cocaine on blood-brain barrier (BBB) integrity has also been reported. This study evaluates the effects of repeated social defeat (RSD) during adolescence on the reinforcing and motivational effects of cocaine in adult mice and the changes induced by RSD on BBB permeability. Cocaine self-administration, conditioned place preference and quantitative analysis of claudin-5, laminin, collagen-IV and IgG immunoreactivity took place 3 weeks after RSD. Mice socially defeated during adolescence developed conditioned place preference and exhibited reinstated preference with a non-effective dose of cocaine (1 mg/kg). RSD mice needed significantly more sessions than control animals for the preference induced by 25 mg/kg of cocaine to be extinguished. However, acquisition of cocaine self-administration (0.5 mg/kg per injection) was delayed in the RSD group. Mice exposed to RSD displayed significant changes in BBB structure in adulthood, with a marked reduction in expression of the tight junction protein claudin-5 and an increase in basal laminin degradation (reflected by a decrease in laminin and collagen-IV expression) in the nucleus accumbens and hippocampus. The detrimental effect induced by cocaine (25 mg/kg) on collagen-IV expression in the hippocampus was more pronounced in RSD mice. In summary, our findings suggest that stress and cocaine can increase the long-term vulnerability of the brain to subsequent environmental insults as a consequence of a sustained disruption of the BBB.
dc.description.sponsorship This work was supported by the Spanish Ministerio de Economía y Competitividad ‘Instituto de Salud Carlos III’, RETICS: RD12/0028/0005, RD12/0028/0023, RD12/0028/0002, PSI2011-24762, PSI2014-51847-R, SAF2011-29864 and SAF2013-40592-R. It is also supported by the Catalan Government (2014SGR1547) and the Valenciano Government (PROMETEOII/2014/063). The research leading to these results has also received funding from the European Community’s Seventh Framework Programme (NEUROPAIN, HEALTH-F2-2013)
dc.format.mimetype application/pdfca
dc.identifier.citation Rodríguez-Arias M, Montagud-Romero S, Rubio-Araiz A, Aguilar Morón MA, Martín García E, Cabrera Ortega R et al. Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier. Addict Biol. 2017 Jan;22(1):129-41. DOI: 10.1111/adb.12301
dc.identifier.doi http://dx.doi.org/10.1111/adb.12301
dc.identifier.issn 1355-6215
dc.identifier.uri http://hdl.handle.net/10230/32084
dc.language.iso eng
dc.publisher Wileyca
dc.relation.ispartof Addiction Biology. 2017 Jan;22(1):129-41
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602891
dc.rights This is the pre-peer reviewed version of the following article: Rodríguez-Arias M, Montagud-Romero S, Rubio-Araiz A, Aguilar MA, Martín-García E, Cabrera R et al. Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier. Addict Biol. 2017 Jan; 22(1): 129-141, which has been published in final form at http://dx.doi.org/10.1111/adb.12301. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Estrès
dc.subject.other Cocaïnomania
dc.subject.other Cocaïna -- Efectes fisiològics
dc.title Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrierca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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