Fenofibrate (a PPAR-α Agonist) Administered During Ethanol Withdrawal Reverts Ethanol-Induced Astrogliosis and Restores the Levels of Glutamate Transporter in Ethanol-Administered Adolescent Rats
Autor
Villavicencio-Tejo, Francisca
Flores-Bastías, Osvaldo
Marambio-Ruiz, Lucas
Pérez-Reytor, Diliana Celeste
Karahanian, Eduardo
Resumen
High-ethanol intake induces a neuroinflammatory response, which has been proposed as responsible for the maintenance of chronic ethanol consumption. Neuroinflammation decreases glutamate transporter (GLT-1) expression, increasing levels of glutamate that trigger dopamine release at the corticolimbic reward areas, driving long-term drinking behavior. The activation of peroxisome proliferator-activated receptor alpha (PPARα) by fibrates inhibits neuroinflammation, in models other than ethanol consumption. However, the effect of fibrates on ethanol-induced neuroinflammation has not yet been studied. We previously reported that the administration of fenofibrate to ethanol-drinking rats decreased ethanol consumption. Here, we studied whether fenofibrate effects are related to a decrease in ethanol-induced neuroinflammation and to the normalization of the levels of GLT-1. Rats were administered ethanol on alternate days for 4 weeks (2 g/kg/day). After ethanol withdrawal, fenofibrate was administered for 14 days (50 mg/kg/day) and the levels of glial fibrillary acidic protein (GFAP), phosphorylated NF-κB-inhibitory protein (pIκBα) and GLT-1, were quantified in the prefrontal cortex, hippocampus, and hypothalamus. Ethanol treatment increased the levels of GFAP in the hippocampus and hypothalamus, indicating a clear astrocytic activation. Similarly, ethanol increased the levels of pIκBα in the three areas. The administration of fenofibrate decreased the expression of GFAP and pIκBα in the three areas. These results indicate that fenofibrate reverts both astrogliosis and NF-κB activation. Finally, ethanol decreased GLT-1 expression in the prefrontal cortex and hippocampus. Fenofibrate normalized the levels of GLT-1 in both areas, suggesting that its effect in reducing ethanol consumption could be due to the normalization of glutamatergic tone.
Colecciones
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Article
Fenofibrate Decreases Ethanol-Induced Neuroinflammation and Oxidative Stress and Reduces Alcohol Relapse in Rats by a PPAR-α-Dependent Mechanism (2024)
Ibáñez, Cristina; Acuña, Tirso; Quintanilla, María Elena; Pérez-Reytor, Diliana; Morales, Paola; Karahanian, Eduardo (Multidisciplinary Digital Publishing Institute (MDPI), 2023)High ethanol consumption triggers neuroinflammation, implicated in sustaining chronic alcohol use. This inflammation boosts glutamate, prompting dopamine release in reward centers, driving prolonged drinking and relapse. ... -
Article
Fenofibrate-a pparα agonist-increases alcohol dehydrogenase levels in the liver: Implications for its possible use as an ethanol-aversive drug [Fenofibrato-un agonista de pparα-incrementa los niveles de la alcohol deshidrogenasa hepática: Implicaciones para su posible uso como una droga aversiva al etanol] (2020)
Muñoz D.; Rivera-Meza M.; Flores-Bastías O.; Quintanilla M.E.; Karahanian E. (Edita Socidrogalcohol, 2020) -
Review
Activation of Melanocortin-4 Receptor Inhibits Both Neuroinflammation Induced by Early Exposure to Ethanol and Subsequent Voluntary Alcohol Intake in Adulthood in Animal Models: Is BDNF the Key Mediator? (2020)
Flores-Bastías O.; Adriasola-Carrasco A.; Karahanian E. (Frontiers Media S.A., 2020)