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dc.contributor.authorCastilla Ortega, Estela
dc.contributor.authorBlanco Calvo, Eduardo
dc.contributor.authorSerrano, Antonia
dc.contributor.authorLadrón de Guevara-Miranda, David
dc.contributor.authorPedraz, María
dc.contributor.authorEstivill Torrús, Guillermo
dc.contributor.authorPavón, Francisco Javier
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorSantín Núñez, Luis Javier
dc.date.accessioned2016-01-25T17:02:59Z
dc.date.issued2015-03-14
dc.identifier.issn1355-6215
dc.identifier.urihttp://hdl.handle.net/10459.1/49385
dc.description.abstractWe investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesisreduced mice showed normal CPP acquisition but engaged an alternate brain circuitwhere the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus)were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherJohn Wiley & Sons
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1111/adb.12248
dc.relation.ispartofAddiction Biology, 2015, p. 1-14
dc.rights(c) Society for the Study of Addiction, 2015
dc.subjectBrain networks connectivity
dc.subjectDrug addiction vulnerability
dc.subjectEarly immediate gene C-Fos
dc.subjectExtinction and reinstatement
dc.subjectPrincipal components factorial analysis
dc.subject.classificationCocaïna
dc.subject.classificationHipocamp (Cervell)
dc.subject.otherCocaine
dc.subject.otherHippocampus (Brain)
dc.titlePharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2016-01-25T17:03:00Z
dc.identifier.idgrec024943
dc.type.versionpublishedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.identifier.doihttps://doi.org/10.1111/adb.12248
dc.date.embargoEndDate10000-01-01


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