Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production
Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production
复制标题
小鼠乙醇刺激行为受脑过氧化氢酶活性和 H2O2 生成率调节
作者：
R. Pastor;C. Sanchis‐Segura;C. Aragón
摘要
基本原理。在过去的几年里，大脑过氧化氢酶-过氧化氢酶系统在给药后观察到的啮齿类动物的行为影响中被认为是一个角色。这一作用似乎与大脑过氧化氢酶利用过氧化氢作为共底物将乙醇代谢为乙醛的能力有关。另一方面，已有研究表明，在活体内，常压高氧增加了啮齿类动物大脑中过氧化氢的产生速度。因此，底物水平的变化可以调节大脑的过氧化氢酶活性，从而调节乙醇的行为效应。
目标。本研究的目的是评估高氧暴露后大脑过氧化氢产生的增加是否导致乙醇诱导的小鼠运动增加。
方法：研究方法。CD-1小鼠暴露于空气或99.5%O2吸入(15、30或45分钟)和处理后0、30、60或120分钟后，测量乙醇诱导的运动。注射3-氨基-1，2，4-三氮唑后，过氧化氢介导的内源性脑组织过氧化氢酶活性失活被用来衡量脑组织产生过氧化氢的速率。
结果。高氧暴露(30或45分钟)增强乙醇(2.5或3.0 mg/kg)的运动刺激效应，而可卡因(4 mg/kg)或咖啡因(15 mg/kg)诱导的运动和血液酒精水平不受影响。此外，研究结果还证实了小鼠大脑中过氧化氢的过量产生。
结论。目前的结果表明，大脑过氧化氢产生的增加加强了乙醇诱导的运动。因此，这项研究进一步支持了大脑过氧化氢酶-过氧化氢系统，以及由此暗示的集中形成的乙醛，在乙醇的精神药理作用的中介中发挥关键作用的观点。
Abstract
Rationale. Over the last few years, a role for the brain catalase-H2O2 enzymatic system has been suggested in the behavioural effects observed in rodents after ethanol administration. This role seems to be related to the ability of cerebral catalase to metabolise ethanol to acetaldehyde using H2O2 as a co-substrate. On the other hand, it has been shown that normobaric hyperoxia increases the rate of cerebral H2O2 production in rodents in vivo. Thus, substrate-level changes could regulate brain catalase activity, thereby modulating the behavioural effects of ethanol.
Objectives. The aim of the present study was to assess if the enhancement of cerebral H2O2 production after hyperoxia exposure results in a boost of ethanol-induced locomotion in mice.
Methods. CD-1 mice were exposed to air or 99.5% O2 inhalation (for 15, 30, or 45 min) and 0, 30, 60 or 120 min after this treatment, ethanol-induced locomotion was measured. The H2O2-mediated inactivation of endogenous brain catalase activity following an injection of 3-amino-1,2,4-triazole was used as a measure of the rate of cerebral H2O2 production.
Results. Hyperoxia exposure (30 or 45 min) potentiated the locomotor-stimulating effects of ethanol (2.5 or 3.0 g/kg), whereas cocaine (4 mg/kg) or caffeine (15 mg/kg)-induced locomotion and blood ethanol levels were unaffected. Moreover, the results also confirmed brain H2O2 overproduction in mice.
Conclusions. The present results suggest that an increase in brain H2O2 production potentiates ethanol-induced locomotion. Therefore, this study provides further support for the notion that the brain catalase-H2O2 system, and by implication centrally formed acetaldehyde, plays a key role in the mediation of ethanol's psychopharmacological effects.
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