Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine

• Autor(a) principal: Maria Carolina Machado da Silva
• Data de Publicação: 2021
• Outros Autores: Giovanni Freitas Gomes, Heliana de Barros Fernandes, Aristóbolo Mendes da Silva, Antônio Lucio Teixeira Junior, Fabrício de Araújo Moreira, Aline Silva de Miranda, Antônio Carlos Pinheiro de Oliveira
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.1038/s41598-021-95059-7; http://hdl.handle.net/1843/54935; https://orcid.org/0000-0002-0200-2902; https://orcid.org/0000-0002-4855-3056; https://orcid.org/0000-0001-7473-7433; https://orcid.org/0000-0002-9621-5422; https://orcid.org/0000-0002-0824-7302; https://orcid.org/0000-0003-2811-7924; https://orcid.org/0000-0003-3217-4294
• topic: CSF1R; Microglia; Cocaine; Microglia; Transtornos relacionados ao uso de substâncias; Cocaína

Diferent data suggest that microglia may participate in the drug addiction process as these cells respond to neurochemical changes induced by the administration of these substances. In order to study the role of microglia in drug abuse, Swiss mice aged 8–9 weeks were treated with the CSF1R inhibitor PLX3397 (40 mg/kg, p.o.) and submitted to behavioral sensitization or conditioned place preference (CPP) induced by cocaine (15 mg/kg, i.p.). Thereafter, brains were used to evaluate the efects of CSF1R inhibition and cocaine administration on morphological, biochemical and molecular changes. CSF1R inhibition attenuated behavioral sensitization, reduced the number of Iba-1+ cells and increased ramifcation and lengths of the branches in the remaining microglia. Additionally, both cocaine and PLX3397 increased the cell body to total cell size ratio of Iba-1+ cells, as well as CD68+ and GFAP+ stained areas, suggesting an activated pattern of the glial cells. Besides, CSF1R inhibition increased CX3CL1 levels in the striatum, prefrontal cortex and hippocampus, as well as reduced CX3CR1 expression in the hippocampus. In this region, cocaine also reduced BDNF levels, an efect that was enhanced by CSF1R inhibition. In summary, our results suggest that microglia participate in the behavioral and molecular changes induced by cocaine. This study contributes to the understanding of the role of microglia in cocaine addiction.