RT Journal Article
T1 Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain
A1 Aranda, Jesús
A1 Fernández-Arjona, María del Mar
A1 Alén, Francisco
A1 Rivera-González, Patricia
A1 Rubio-Lamia, Leticia Olga
A1 Smith-Fernández, Inés María
K1 Alcohol
AB Preclinical studies on the efects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication oftenprescribed 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 afterresuming 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 increasedmicroglial 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 modifedmicroglial 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 changesin mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1β, IL6, IL10) andthe innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifcally, TLR4 correlated with microglial spatialcomplexity assessed by fractal dimension in striatum, suggesting a role in process branching. (...)
PB Springer
YR 2021
FD 2021-07-08
LK https://hdl.handle.net/10630/24020
UL https://hdl.handle.net/10630/24020
LA eng
NO Aranda, 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/s00429-021-02321-9
NO Open 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; inthe collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026