Microglia-mediated calcium-permeable AMPAR accumulation in the nucleus accumbens drives hyperlocomotion during cocaine withdrawal.

Autor: Reverte I; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Marchetti C; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Pezza S; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Zenoni SF; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Scaringi G; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Ferrucci L; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., D'Ottavio G; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy., Pignataro A; IRCCS Santa Lucia Foundation, Rome, Italy; Institute of Translational Pharmacology, National Research Council, CNR, Rome, Italy., Andolina D; IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy., Raspa M; National Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus 'A. Buzzati-Traverso', Monterotondo (Rome), Italy., Scavizzi F; National Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus 'A. Buzzati-Traverso', Monterotondo (Rome), Italy., Venniro M; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, USA., Ramsey LA; Behavioral Neuroscience Research Branch, Intramural Research Program, Baltimore NIDA, NIH, USA., Gross C; Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy., Caprioli D; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address: daniele.caprioli@uniroma1.it., Ragozzino D; Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Jan; Vol. 115, pp. 535-542. Date of Electronic Publication: 2023 Nov 13.
DOI: 10.1016/j.bbi.2023.11.007
Abstrakt: During withdrawal from cocaine, calcium permeable-AMPA receptors (CP-AMPAR) progressively accumulate in nucleus accumbens (NAc) synapses, a phenomenon linked to behavioral sensitization and drug-seeking. Recently, it has been suggested that neuroimmune alterations might promote aberrant changes in synaptic plasticity, thus contributing to substance abuse-related behaviors. Here, we investigated the role of microglia in NAc neuroadaptations after withdrawal from cocaine-induced conditioned place preference (CPP). We depleted microglia using PLX5622-supplemented diet during cocaine withdrawal, and after the place preference test, we measured dendritic spine density and the presence of CP-AMPAR in the NAc shell. Microglia depletion prevented cocaine-induced changes in dendritic spines and CP-AMPAR accumulation. Furthermore, microglia depletion prevented conditioned hyperlocomotion without affecting drug-context associative memory. Microglia displayed fewer number of branches, resulting in a reduced arborization area and microglia control domain at late withdrawal. Our results suggest that microglia are necessary for the synaptic adaptations in NAc synapses during cocaine withdrawal and therefore represent a promising therapeutic target for relapse prevention.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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