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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-Valle, Cristina
dc.contributor.authorEstivill-Torrús, Guillermo
dc.contributor.authorSerrano, Antonia
dc.contributor.authorPavón, Francisco Javier
dc.contributor.authorRodríguez de Fonseca, Fernándo
dc.contributor.authorSantin-Nuñez, Luis Javier 
dc.contributor.authorCastilla Ortega, María Estela
dc.date.accessioned2022-03-07T13:30:14Z
dc.date.available2022-03-07T13:30:14Z
dc.date.issued2019
dc.identifier.citationLadrón de Guevara-Miranda D, Moreno-Fernández RD, Gil-Rodríguez S, Rosell-Valle C, Estivill-Torrús G, Serrano A, Pavón FJ, Rodríguez de Fonseca F, Santín LJ, Castilla-Ortega E. Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory. Addict Biol. 2019 May;24(3):458-470. doi: 10.1111/adb.12612. Epub 2018 Feb 26. PMID: 29480526.es_ES
dc.identifier.urihttps://hdl.handle.net/10630/23841
dc.descriptionAuthor manuscriptes_ES
dc.description.abstractErasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (a LPA1/3 receptor antagonist), or a vehicle solution, and they were tested 23 days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA-treated mice exhibited reduced long-term CPP retention and an ~two-fold increase in the number of adult-born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425-treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety-like responses. In a second experiment, normal and LPA1 receptor-deficient mice were acutely infused with LPA, which revealed that LPA1-mediated signaling was required for LPA-induced proliferative actions. These results suggest that the LPA/LPA1-pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro-AHN strategies to treat aberrant cognition in those addicted to cocaine.es_ES
dc.description.sponsorshipThis study was funded by grants from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación), which is cofunded by the European Research Development Fund AEI/FEDER, UE- (PSI2013-44901-P and PSI2017-82604-R to LJS and PSI2015-73156-JIN to ECO); 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 FRdF); and by the Andalusian R&D&I Programme, Regional Ministry of Economy and Knowledge (PAIDI CTS643 to GET). DLGM and RDMF hold FPU grants from the Spanish Ministry of Education, Culture and Sports (FPU13/04819 and FPU14-01610, respectively). CRV received a ‘Plan Propio’ grant from the University of Malaga. FJP and AS hold ‘Miguel Servet’ grants (CP14/00212 and CP14/00173, respectively) from the National System of Health-Instituto de Salud Carlos III, which is co-funded by AEI/FEDER, UE. FRdF and GET are supported by Nicolas Monardes Programme, from the Andalusian Regional Ministry of Health. ECO 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 European Research Development Fund (AEI/FEDER, UE).es_ES
dc.language.isoenges_ES
dc.publisherWileyes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectNeurobiología del desarrolloes_ES
dc.subjectHipocampo (Cerebro)es_ES
dc.subject.otherAntagonist ki16425es_ES
dc.subject.otherAnxietyes_ES
dc.subject.otherCausal mediation analysises_ES
dc.subject.otherCell proliferationes_ES
dc.subject.otherConditioned place preference CPPes_ES
dc.subject.otherLPA1 receptores_ES
dc.titleLysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memoryes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.centroFacultad de Psicologíaes_ES
dc.identifier.doi10.1111/adb.12612
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersiones_ES


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