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Reverte, Ingrid; Marchetti, Claudia; Pezza, Sara; Zenoni, Soami F; Scaringi, Giorgia; Ferrucci, Laura; D'Ottavio, Ginevra; Pignataro, Annabella; Andolina, Diego; Raspa, Marcello; Scavizzi, Ferdinando; Venniro, Marco; Ramsey, Leslie A; Gross, Cornelius; Caprioli, Daniele; Ragozzino, Davide
Brain, behavior, and immunity, 01/2024, Letnik: 115Journal Article
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.
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