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dc.contributor.authorLadrón de Guevara-Miranda, David
dc.contributor.authorMoreno-Fernández, Román D.
dc.contributor.authorGil-Rodríguez, Sara
dc.contributor.authorRosell-del-Valle, Cristina
dc.contributor.authorEstivill-Torrús, Guillermo
dc.contributor.authorSerrano, Antonia
dc.contributor.authorPavón, Francisco Javier
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorSantin-Nuñez, Luis Javier 
dc.contributor.authorCastilla Ortega, María Estela
dc.date.accessioned2018-06-28T06:10:26Z
dc.date.available2018-06-28T06:10:26Z
dc.date.created2018
dc.date.issued2018-06-28
dc.identifier.urihttps://hdl.handle.net/10630/16027
dc.description.abstractStimulating adult hippocampal neurogenesis (AHN) has been uncovered as a promising approach in the manipulation of retrograde memories. This work aims to study whether increasing AHN with lysophosphatidic acid (LPA, an endogenous lysophospholipid with proneurogenic actions) promotes the forgetting of previously established cocaine-contextual associations. C57BL/6J mice previously trained in a cocaine-induced conditioned place preference (CPP) paradigm were submitted to 23 days of withdrawal, during which they received repeated intracerebroventricular infusions of LPA, ki16425 (a selective LPA1/3 receptors antagonist), or vehicle solution. Then, CPP maintenance was assessed, and the causal role of AHN in this process was evaluated using a mediation analysis. In a complementary experiment, wild-type and LPA1-null mice were acutely infused with LPA or ki16425 to determine the involvement of the LPA1 receptor in the in vivo proneurogenic actions of LPA. The chronic LPA treatment significantly weakened the long-term retention of a previously acquired cocaine-CPP memory, an effect clearly mediated by a LPA-induced increase in the number of adult-born dentate granule cells. In contrast, the ki16425-treated mice displayed aberrant responses of initially decreased CPP retention that progressively increased CPP across the extinction sessions, in absence of effects on AHN. The histological studies suggested that the proneurogenic actions of LPA were related to the enhancement of cell proliferation and critically depended on the LPA1 receptor function. Our results suggest that the LPA/LPA1-pathway acts as a potent in vivo modulator of AHN, and highlight the usefulness of a post-learning increase of adult-born hippocampal neurons as a strategy to promote the forgetting of cocaine-context associations.en_US
dc.description.sponsorshipPlan Propio de Investigación y Transferencia. Campus de Excelencia Internacional Andalucía Tech. Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación), co‐funded by the European Research Development Fund (AEI/FEDER, UE) (PSI2013‐44901‐P and PSI2017‐82604‐R to L.J.S. and PSI2015‐73156‐JIN to E.C.O.); by the National System of Health‐Instituto de Salud Carlos III, which is co‐funded by AEI/FEDER, UE (Red de Trastornos Adictivos; RD16/0017/0001 to F.R.d.F.); and by the Andalusian R&D&I Programme, Regional Ministry of Economy and Knowledge (PAIDI CTS643 to G.E.T.). D.L.G.M. hold a FPU grant from the Spanish Ministry of Education, Culture and Sports (FPU13/04819 ). F.R.d.F. and G.E.T. are supported by Nicolas Monardes Programme, from the Andalusian Regional Ministry of Health. E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015‐73156‐JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación), which is co‐funded by the AEI/FEDER, UE.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNeurogénesisen_US
dc.subjectMemoriaen_US
dc.subject.otherConditioned place preferenceen_US
dc.subject.otherLPA1 receptoren_US
dc.subject.otherAntagonist ki16425en_US
dc.subject.otherAnxietyen_US
dc.subject.otherCausal mediation analysisen_US
dc.titleEnhancing adult hippocampal neurogenesis with lysophosphatidic acid: a proposal for erasing cocaine contextual memoryen_US
dc.typeinfo:eu-repo/semantics/conferenceObjecten_US
dc.centroFacultad de Psicologíaen_US
dc.relation.eventtitle31st CINP World Congressen_US
dc.relation.eventplaceVienaen_US
dc.relation.eventdate16/06/2018en_US


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