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dc.contributor.authorAranda, Jesús
dc.contributor.authorFernández-Arjona, María del Mar
dc.contributor.authorAlén, Francisco
dc.contributor.authorRivera, Patricia
dc.contributor.authorRubio, Leticia
dc.contributor.authorSmith-Fernández, Inés María 
dc.date.accessioned2022-05-03T10:05:54Z
dc.date.available2022-05-03T10:05:54Z
dc.date.issued2021-07-08
dc.identifier.citationAranda, J., Fernández-Arjona, M., Alén, F. et al. Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain. Brain Struct Funct 226, 2243–2264 (2021). https://doi.org/10.1007/s00429-021-02321-9es_ES
dc.identifier.urihttps://hdl.handle.net/10630/24020
dc.description.abstractPreclinical studies on the efects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication often prescribed in alcohol use disorder (AUD) patients with depression, results in alcohol consumption escalation after resuming drinking. However, a potential neuroinfammatory component on this escalation remains unexplored despite the immunomodulatory role of serotonin. Here, we utilized a rat model of 14-daily administration of the SSRI fuoxetine (10 mg/kg/day) along alcohol self-administration deprivation to study the efects of fuoxetine cessation on neuroinfammation after resuming alcohol drinking. Microglial morphology and infammatory gene expression were analyzed in prelimbic cortex, striatum, basolateral amygdala and dorsal hippocampus. Results indicated that alcohol drinking reinstatement increased microglial IBA1 immunoreactivity and altered morphometric features of activated microglia (fractal dimension, lacunarity, density, roughness, and cell area, perimeter and circularity). Despite alcohol reinstatement, fuoxetine cessation modifed microglial morphology in a brain region-specifc manner, resulting in hyper-ramifed (spatial complexity of branching), reactive (lower heterogeneity and circularity)-like microglia. We also found that microglial cell area correlated with changes in mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1β, IL6, IL10) and the innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifcally, TLR4 correlated with microglial spatial complexity assessed by fractal dimension in striatum, suggesting a role in process branching. (...)es_ES
dc.description.sponsorshipOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for open access charge: Universidad de Málaga/CBUA. RETICS Red de Trastornos Adictivos, Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU) (Grant No. RD16/0017/0001); ISCIII, ERDF-EU (Grant No. PI17/02026, Grant No. PI19/01577); Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas (Grant No. PND 2020/048, Grant No. PND 2019/040, Grant No. PND 2018/044, Grant No. PND 2018/033); and Consejería de Salud y Familia, Junta de Andalucía (Neuro-RECA, Grant No. RIC-0111–2019). JS (Grant No. CPII17/00024), FJP (Grant No. CPII19/00022) and AS (Grant No. CPII19/00031) hold “Miguel Servet II” research contracts from the National System of Health, ISCIII, ERDF-EU. FJP also holds a “Nicolas Monardes” contract from Servicio Andaluz de Salud, Consejería de Salud y Familia, Junta de Andalucía (Grant No. C1-0049–2019). PR (Grant No. CP19/00068) hold “Miguel Servet I” research contracts from the National System of Health, ISCIII, ERDF-EU. The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.es_ES
dc.language.isoenges_ES
dc.publisherSPRINGERes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAlcoholes_ES
dc.subject.otherAntidepressantes_ES
dc.subject.otherHippocampuses_ES
dc.subject.otherInfammationes_ES
dc.subject.otherMicrogliaes_ES
dc.subject.otherFractal dimensiones_ES
dc.titleSudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat braines_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.centroFacultad de Cienciases_ES
dc.identifier.doihttps://doi.org/10.1007/s00429-021-02321-9
dc.rights.ccAtribución 4.0 Internacional*


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