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https://doi.org/10.1016/j.biopha.2023.115055
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Título: | Morphine-withdrawal aversive memories and their extinction modulate H4K5 acetylation and Brd4 activation in the rat hippocampus and basolateral amygdala |
Fecha de publicación: | jun-2023 |
Cita bibliográfica: | Biomedicine & Pharmacotherapy 165 (2023) 115055. |
ISSN: | 0753-3322 1950-6007 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::615 - Farmacología. Terapéutica. Toxicología. Radiología |
Palabras clave: | Opioid aversive memories Extinction Epigenetic marks Brd4 Basolateral amygdala Hippocampus |
Resumen: | Chromatin modification is a crucial mechanism in several important phenomena in the brain, including drug addiction. Persistence of drug craving and risk of relapse could be attributed to drug-induced epigenetic mechanisms that seem to be candidates explaining long-lasting drug-induced behaviour and molecular alterations. Histone acetylation has been proposed to regulate drug-seeking behaviours and the extinction of rewarding memory of drug taking. In this work, we studied the epigenetic regulation during conditioned place aversion and after extinction of aversive memory of opiate withdrawal. Through immunofluorescence assays, we assessed some epigenetic marks (H4K5ac and p-Brd4) in crucial areas related to memory retrieval -basolateral amygdala (BLA) and hippocampus-. Additionally, to test the degree of transcriptional activation, we evaluated the immediate early genes (IEGs) response (Arc, Bdnf, Creb, Egr-1, Fos and Nfkb) and Smarcc1 (chromatin remodeler) through RT-qPCR in these nuclei. Our results showed increased p-Brd4 and H4K5ac levels during aversive memory retrieval, suggesting a more open chromatin state. However, transcriptional activation of these IEGs was not found, therefore suggesting that other secondary response may already be happening. Additionally, Smarcc1 levels were reduced due to morphine chronic administration in BLA and dentate gyrus. The activation markers returned to control levels after the retrieval of aversive memories, revealing a more repressed chromatin state. Taken together, our results show a major role of the tandem H4K5ac/p-Brd4 during the retrieval of aversive memories. These results might be useful to elucidate new molecular targets to improve and develop pharmacological treatments to address addiction and to avoid drug relapse. |
Autor/es principal/es: | Franco García, Aurelio Gómez Murcia, Victoria Fernández Gómez, Francisco José González Andreu, Raúl Hidalgo Céspedes, Juana María Milanes Maquilón, María Victoria Núñez Parra, María Cristina |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Farmacología |
URI: | http://hdl.handle.net/10201/132543 |
DOI: | https://doi.org/10.1016/j.biopha.2023.115055 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 15 |
Derechos: | info:eu-repo/semantics/openAccess |
Descripción: | © 2023 The Authors. Published by Elsevier Masson SAS. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomedicine & Pharmacotherapy. To access the final edited and published work see https://doi.org/10.1016/j.biopha.2023.115055 |
Aparece en las colecciones: | Artículos: Farmacología |
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