Anxiogenic and stress-inducing effects of peripherally administered acetaldehyde in mice: Similarities with the disulfiram-ethanol reaction
Anxiogenic and stress-inducing effects of peripherally administered acetaldehyde in mice: Similarities with the disulfiram-ethanol reaction
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DOI：
10.1016/j.pbb.2011.10.002
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Correa, Merce
中科院分区：
文献类型：
--
作者：
Escrig, Miguel A.;Pardo, Marta;Correa, Merce
乙醇的第一代谢产物乙醛的外周积累在人体中产生称为“潮红”的自主反应。在一些醛脱氢酶（ALDH 2）活性较低的人群中观察到的潮红的厌恶特征是用双硫仑治疗酗酒者的基础。ALDH抑制剂。虽然乙醇和中央形成的乙醛具有抗焦虑作用，外周积累的乙醛可能是令人厌恶的，部分原因是它是anxiogenic.Objectives：我们研究了直接管理的乙醛对焦虑的行为措施和应激小鼠的激素标志物的影响。评价双硫仑对乙醇抗焦虑作用的影响。方法：CD 1雄性小鼠在不同时间间隔分别接受乙醛（0，25，50，75或100 mg/kg），并在高架十字迷宫和暗光箱中进行评估。还评估了乙醛给药后皮质酮的释放。额外的实验评估的影响，双硫仑的抗焦虑作用的乙醇（0或1毫克/公斤），和乙酸的效果上加迷宫.Results：乙醛（100毫克/公斤）的直接管理在1，11或26分钟后IP管理有致焦虑作用。乙醛在诱导皮质酮释放方面的效力是乙醇的10倍。双硫仑本身不影响行为，但在30和60 mg/kg剂量下阻断乙醇的抗焦虑作用，当与乙醇联合给药时，在最高剂量（90 mg/kg）下具有致焦虑作用。醋酸没有影响任何的焦虑parameters.Conclusions：外周管理或积累的乙醛产生焦虑的影响，并诱导内分泌应激反应。这种作用不是由其代谢物醋酸盐介导的。(C)2011 Elsevier Inc. All rights reserved.
Peripheral accumulation of acetaldehyde, the first metabolite of ethanol, produces autonomic responses in humans called "flushing". The aversive characteristics of flushing observed in some populations with an isoform of aldehyde dehydrogenase (ALDH2) less active, are the basis for treating alcoholics with disulfiram. an ALDH inhibitor. Although ethanol and centrally formed acetaldehyde have anxiolytic effects, peripheral accumulation of acetaldehyde may be aversive in part because it is anxiogenic.Objectives: We investigated the effect of direct administration of acetaldehyde on behavioral measures of anxiety and on hormonal markers of stress in mice. The impact of disulfiram on the anxiolytic actions of ethanol was evaluated. Acetate (a metabolite of acetaldehyde) was also studied.Methods: CD1 male mice received acetaldehyde (0, 25, 50, 75 or 100 mg/kg) at different time intervals and were assessed in the elevated plus maze and in the dark-light box. Corticosterone release after acetaldehyde administration was also assessed. Additional experiments evaluated the impact of disulfiram on the anxiolytic effect of ethanol (0 or 1 mg/kg), and the effect of acetate on the plus maze.Results: Direct administration of acetaldehyde (100 mg/kg) had an anxiogenic effect at 1, 11 or 26 min after IP administration. Acetaldehyde was ten times more potent than ethanol at inducing corticosterone release. Disulfiram did not affect behavior on its own, but blocked the anxiolytic effect of ethanol at doses of 30 and 60 mg/kg, and had an anxiogenic effect at the highest dose (90 mg/kg) when co-administered with ethanol. Acetate did not affect any of the anxiety parameters.Conclusions: Peripheral administration or accumulation of acetaldehyde produces anxiogenic effects and induces endocrine stress responses. This effect is not mediated by its metabolite acetate. (C) 2011 Elsevier Inc. All rights reserved.