The H₂O₂ scavenger ebselen decreases ethanol-induced locomotor stimulation in mice

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• 作者：Juan Carlos Ledesma ; Laura Font ; Carlos M.G. Aragon ; ^{aragon@psb.uji.es}
• 关键词：Ethanol ; Ebselen ; H2O2 ; Catalase ; Acetaldehyde ; Locomotor stimulation
• 刊名：Drug and Alcohol Dependence
• 出版年：2012
• 期刊代码：81_03768716
• 类别：med
• 出版时间：1 July, 2012
• 卷：124
• 期：1-2
• 页码：42-49
• 文件大小：697 K

摘要

Background

In the brain, the enzyme catalase by reacting with H₂O₂ forms Compound I (catalase-H₂O₂ system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H₂O₂ in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H₂O₂ scavenger, on ethanol-induced locomotion.

Methods

Swiss RjOrl mice were pre-treated with ebselen (0-50 mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75 g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25 mg/kg; IP) before caffeine (15 mg/kg; IP), amphetamine (2 mg/kg; IP) or cocaine (10 mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H₂O₂-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT).

Results

Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity.

Conclusions

Taken together, these data suggest that a decline in H₂O₂ levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H₂O₂ in some of the psychopharmacological effects produced by ethanol.