title: Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration.
abstract: Alcohol abuse is frequently characterized by a specific pattern of intake in binge drinking episodes, inducing neuroinflammation and brain damage. Here, we characterized the temporal profile of neuroinflammation in rats exposed to intragastric binge ethanol administrations (3 times/day × 4 days) and tested the anti-inflammatory/neuroprotective properties of the satiety factor oleoylethanolamide (OEA). Pre-treatment with OEA (5 mg/kg, i.p.) previous each alcohol gavage blocked the expression of high mobility group box 1 (HMGB1) danger signal and the innate immunity Toll-like receptors 4 (TLR4) in frontal cortex, and inhibited the nuclear factor-kappa B (NF-kB) proinflammatory cascade induced by alcohol binge administration. OEA reduced the levels of interleukin-1beta (IL-1β), the monocyte chemoattractant protein-1 (MCP-1), and the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in ethanol binged animals. Elevations in plasma tumor necrosis factor alpha (TNF-α) and IL-1β after ethanol were also inhibited by OEA. OEA also prevented ethanol-induced lipid peroxidation, caspase-8 and pro-apoptotic caspase-3 activation in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone levels after ethanol with no alteration in blood ethanol levels and may affect ethanol-induced gut permeability for endotoxin. Finally, OEA, administered as a pre-treatment during the ethanol binge, exerted antidepressant-like effects during acute withdrawal. Altogether, results highlight a beneficial profile of OEA as a potent anti-inflammatory, antioxidant, neuroprotective and antidepressant-like compound to treat alcohol abuse.
authors: Department of Psychobiology, Faculty of Psychology, Complutense University, Spain.
authors: María
authors: M
authors: Antón
authors: Department of Psychobiology, Faculty of Psychology, Complutense University, Spain.
authors: Francisco
authors: F
authors: Alén
authors: Department of Psychobiology, Faculty of Psychology, Complutense University, Spain.
authors: Raquel
authors: R
authors: Gómez de Heras
authors: Instituto de Investigación Biomédica (IBIMA), Málaga, and Red de Trastornos Adictivos (RTA), Spain.
authors: Antonia
authors: A
authors: Serrano
authors: Instituto de Investigación Biomédica (IBIMA), Málaga, and Red de Trastornos Adictivos (RTA), Spain.
authors: Francisco Javier
authors: FJ
authors: Pavón
authors: Department of Pharmacology, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) & Imas12, Spain.
authors: Juan Carlos
authors: JC
authors: Leza
authors: Department of Pharmacology, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) & Imas12, Spain.
authors: Borja
authors: B
authors: García-Bueno
authors: Department of Psychobiology, Faculty of Psychology, Complutense University, Spain.|Instituto de Investigación Biomédica (IBIMA), Málaga, and Red de Trastornos Adictivos (RTA), Spain.
authors: Fernando
authors: F
authors: Rodríguez de Fonseca
authors: Department of Psychobiology, Faculty of Psychology, Complutense University, Spain.
authors: Laura
authors: L
authors: Orio
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000150:complications*; D003866:Depressive Disorder / Q000139:chemically induced* / Q000517:prevention & control; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D024243:HMGB1 Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects; D009829:Oleic Acids / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D063388:Endocannabinoids; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D016328:NF-kappa B; D009829:Oleic Acids; D051197:Toll-Like Receptor 4; C488250:oleoylethanolamide; D000431:Ethanol
keywords: Alcohol binge; HMGB1; TLR4; neuroinflammation; neuroprotection; oleoylethanolamide