Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents
Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents
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DOI：
10.1007/s00213-008-1219-3
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Aragon, C. M. G.
中科院分区：
文献类型：
--
作者：
Correa, M.;Manrique, H. M.;Aragon, C. M. G.
相当多的证据表明，脑乙醇代谢介导的过氧化氢酶参与调节这种药物的一些行为和生理作用，这表明，乙醇的第一代谢产物，乙醛，可能有中枢作用。以前的研究结果表明，乙醛给药到侧脑室产生抗焦虑作用在一个新的开放竞技场在rats.Objectives本研究探讨了中枢形成的乙醛对乙醇诱导的抗焦虑作用的影响。（SA; 0或10 mg/kg，IP）对乙醇诱导的抗焦虑作用（0.0、0.5或1.0 g/kg，IP）在两种焦虑范式（高架十字迷宫和暗/光箱）中在CD 1小鼠中进行评价。额外的研究评估了非竞争性过氧化氢酶抑制剂3-氨基-1，2，4-三唑（AT; 0.5 g/kg，IP）和乙醛失活剂D-青霉胺（50 mg/kg，IP）的效果上加master.Results SA降低了乙醇的抗焦虑作用在高架加迷宫和在黑暗/光箱中评估的几个参数。在加上迷宫，AT完全阻断和D-青霉胺显着降低了anxiolytic properties of ethanol.Conclusions，因此，当大脑代谢的乙醇转化为乙醛被阻断过氧化氢酶抑制剂，或乙醛被灭活，有抑制作用的抗焦虑作用的乙醇。这些数据提供了进一步的支持的想法，中央形成或管理的乙醛可以有助于乙醇的一些精神药理作用，包括其抗焦虑特性。
Rationale Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats.Objectives The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis.Materials and methods The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D-penicillamine (50 mg/kg, IP) on the plus maze.Results SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol.Conclusions Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.