title: Neuro-inflammation induced in the hippocampus of 'binge drinking' rats may be mediated by elevated extracellular glutamate content.
abstract: The neuropathological and immune changes induced in the brain by 'binge drinking' have been investigated in a rat model. Evidence of neuro-inflammation was identified in the 'binge drinking' rat model of alcohol abuse after 3 weeks of administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two consecutive days, followed by 5 days of abstinence: Firstly, alveolar macrophages, isolated from these animals, showed significant increases in inducible nitric oxide synthase, as assayed by nitrite release, both before and after lipopolysaccaharide stimulation. Secondly, significant numbers of activated microglia were present in the dentate gyrus region of the hippocampus of the 'binge drinking' model, after major histocompatibility complex class II staining, by comparison with the control. Microdialysis studies in the ventral hippocampus identified a significant increase in the basal extracellular concentration of glutamate, in both the 2 and 3 g/kg administered 'binge drinking' rats. In contrast, no changes in the hippocampal extracellular concentrations, of GABA and taurine, or the dopamine and serotonin metabolites were observed under basal conditions. A further dose of EtOH induced a significant decrease in the concentrations of both 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid, whereas glutamate, taurine and GABA levels were unaffected. There was no evidence that EtOH preference was initiated by the 'binge drinking' regimen. Our results suggest that the possible toxicity associated with 'binge drinking' maybe directed by the elevated glutamate levels, which in turn, activate phagocytic cells to release their inflammatory cytokines and chemokines, ultimately leading to neuro-inflammation.
authors.affiliation: Dipartimento di Farmacologia Preclinica e Clinica M. Aiazzi Mancini, Università degli Studi di Firenze, Firenze, Italia. wardrobertaj@gmail.com
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Ward
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Colivicchi
authors.forename: Rachel
authors.initials: R
authors.lastname: Allen
authors.forename: François
authors.initials: F
authors.lastname: Schol
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lallemand
authors.forename: Philippe
authors.initials: P
authors.lastname: de Witte
authors.forename: Chiara
authors.initials: C
authors.lastname: Ballini
authors.forename: Laura Della
authors.initials: LD
authors.lastname: Corte
authors.forename: David
authors.initials: D
authors.lastname: Dexter
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000437:Alcoholism / Q000473:pathology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000473:pathology; D017551:Microdialysis / Q000379:methods; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D015306:Biogenic Monoamines; D000949:Histocompatibility Antigens Class II; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D052247:Nitric Oxide Synthase Type II