Ebselen Prevents Chronic Alcohol-Induced Rat Hippocampal Stress and Functional Impairment

Authors

  • Siv Johnsen-Soriano,

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • Francisco Bosch-Morell,

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • María Miranda,

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • Samuel Asensio,

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • Jorge M. Barcia,

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • Joaquín Romá,

    1. Departamento de Fisiología Universitat de València, Valencia, Spain
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  • Pilar Monfort,

    1. Laboratorio de Neurobiología, Centro de Investigación Príncipe Felipe, Valencia, Spain.
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  • Vicente Felipo,

    1. Laboratorio de Neurobiología, Centro de Investigación Príncipe Felipe, Valencia, Spain.
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  • Francisco J. Romero

    1. Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain
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  • This work was supported by Grants PRUCH 04/30 from Fundación San Pablo, from Dirección General de Drogodependencias, Generalitat Valenciana, and from Plan Nacional sobre Drogas, Ministerio de Sanidad, Spain, to FJR, and grants from the Ministerio de Ciencia y Tecnología (SAF2002-00851) and from Ministerio de Sanidad (Red G03-155) of Spain, and from Consellería de Empresa, Universidad y Ciencia, Generalitat Valenciana (Grupos03/001 and GV04B/55) to VF.

Reprint requests: Francisco J. Romero, IDYCA, Research Institute on Drugs and Addictive Behaviours, Universidad CEU-Cardenal Herrera, Av. Seminario s/n, 46113-Moncada, Valencia, Spain. Fax: +34-961-395-272; E-mail: jromero@uch.ceu.es

Abstract

Background: Most of the previously published data suggest a role for oxidative or nitrosative stress in ethanol-induced nervous system damage. Moreover, ethanol is able to impair learning abilities in adult mammalian brain, a process suggested to be directly related to hippocampal neurogenesis. Ebselen, a synthetic compound with antioxidant properties, is able to prevent ethanol-induced impairment of neurogenesis in adult rats. The aim of the present work was to further demonstrate the ability of ebselen to prevent biochemical alterations, and preserve long-term potentiation (LTP) and learning abilities, in the hippocampus of chronic alcoholic adult rats.

Methods: Biochemical markers of oxidative stress (glutathione and malondialdehyde) were assayed in hippocampi of control rats and animals fed a liquid alcoholic diet (Lieber-De Carli) supplemented or not with ebselen. Long-term potentiation and hippocampal-dependent tests were studied in all animal groups.

Results: The hippocampal concentrations of glutathione and malondialdehyde were decreased and increased, respectively, in alcohol-treated animals, and did not differ from those of the control and the alcohol+ebselen groups. Long-term potentiation in hippocampal slices from ethanol-treated animals was prevented, when compared with controls, and occurred with a similar profile in control animals and in the alcohol+ebselen groups. Learning ability was tested with the Morris water maze test. Escape latencies were higher in ethanol-treated rats than in control animals or the ones treated with ethanol+ebselen.

Conclusions: The results herein strongly suggest that oxidative mechanisms may underlie the hippocampal effects of ethanol in adult rats, in view of the protective effect of ebselen.

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