Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory

Addiction Biology
David Ladrón de Guevara-MirandaEstela Castilla-Ortega

Abstract

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 (an 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 approximately twofold 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 ...Continue Reading

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Citations

Sep 24, 2019·Journal of Psychopharmacology·Patricia Sampedro-PiqueroLuis J Santín
Mar 27, 2020·Frontiers in Neuroscience·Cuicui LiChenglin Zhou
Jul 18, 2020·Frontiers in Behavioral Neuroscience·Miguel Á Luján, Olga Valverde
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May 27, 2021·Experimental Biology and Medicine·Gábor TigyiSue Chin Lee

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