Ebselen prevents chronic alcohol-induced rat hippocampal stress and functional impairment.
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.
Johnsen-Soriano
Siv
S
Departamento de Fisiología, Farmacología & Toxicología, Instituto de Drogas y Conductas Adictivas (IDYCA), Universidad CEU-Cardenal Herrera, Moncada, Valencia, Spain.
Bosch-Morell
Francisco
F
Miranda
María
M
Asensio
Samuel
S
Barcia
Jorge M
JM
Romá
Joaquín
J
Monfort
Pilar
P
Felipo
Vicente
V
Romero
Francisco J
FJ
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D054833:Isoindoles; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005978:Glutathione