RT Journal Article
T1 Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory
A1 Ladrón de Guevara-Miranda, David
A1 Moreno-Fernández, Román D.
A1 Gil Rodríguez, Sara
A1 Rosell-del-Valle, Cristina
A1 Estivill-Torrús, Guillermo
A1 Serrano, Antonia
A1 Pavón-Morón, Francisco Javier
A1 Rodriguez-de-Fonseca, Fernando
A1 Santín-Núñez, Luis Javier
A1 Castilla-Ortega, María Estela
K1 Neurobiología del desarrollo
K1 Hipocampo (Cerebro)
AB Erasing 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.
PB Wiley
YR 2019
FD 2019
LK https://hdl.handle.net/10630/23841
UL https://hdl.handle.net/10630/23841
LA eng
NO Ladrón 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.
NO Author manuscript
NO This 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).
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026