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首页> 外文期刊>The European Journal of Neuroscience >Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system.
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Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system.

机译：乙醛介导中脑边缘多巴胺系统的酒精活化。

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摘要

Ethanol (EtOH), the main psychoactive ingredient of alcoholic drinks, is widely considered to be responsible for alcohol abuse and alcoholism through its positive motivational properties, which depend, at least partially, on the activation of the mesolimbic dopaminergic system. However, acetaldehyde (ACD), the first metabolite of EtOH, has been classically considered to be aversive and useful in the pharmacological therapy of alcoholics. Here we show that EtOH-derived ACD is necessary for EtOH-induced place preference, a pre-clinical test with high predictive validity for reward liability. We also found that ACD is essential for EtOH-increased microdialysate dopamine (DA) levels in the rat nucleus accumbens and that this effect is mimicked by intra-ventral tegmental area (VTA) ACD administration. Furthermore, in vitro, ACD enhances VTA DA neuronal firing through action on two ionic currents: reduction of the A-type K+ current and activation of the hyperpolarization-activated inward current. EtOH-stimulating properties on DA neurons are prevented by pharmacological blockade of local catalase, the main metabolic step for biotransformation of EtOH into ACD in the central nervous system. These results provide in-vivo and in-vitro evidence for a key role of ACD in the motivational properties of EtOH and its activation of the mesolimbic DA system. Additionally, these observations suggest that ACD, by increasing VTA DA neuronal activity, would oppose its well-known peripherally originating aversive properties. Careful consideration of these findings could help in devising new effective pharmacological therapies aimed at reducing EtOH intake in alcoholics.
机译：乙醇（EtOH）是酒精饮料的主要精神活性成分，由于其积极的动机特性（至少部分取决于中脑边缘多巴胺能系统的激活），被广泛认为是造成酒精滥用和酗酒的原因。但是，乙醛（ACD）是EtOH的第一种代谢产物，传统上被认为是令人厌恶的，可用于酗酒者的药理学治疗。在这里，我们证明，EtOH诱导的位置偏好是EtOH衍生的ACD所必需的，EtOH诱导的位置偏好是一项临床前测试，对奖励责任具有较高的预测有效性。我们还发现ACD对于大鼠伏隔核中EtOH增加的微透析液多巴胺（DA）水平至关重要，并且腹膜内被盖区（VTA）ACD的给药可模仿这种作用。此外，在体外，ACD通过作用于两种离子电流来增强VTA DA神经元的放电：减少A型K +电流和激活超极化激活的内向电流。药理学上的局部过氧化氢酶的阻滞阻止了DA神经元上EtOH的刺激特性，这是EtOH在中枢神经系统中生物转化为ACD的主要代谢步骤。这些结果提供了体内和体外证据，证明了ACD在EtOH的动机特性及其中脑边缘DA系统的活化中的关键作用。此外，这些观察结果表明，通过增加VTA DA神经元活性，ACD将对抗其众所周知的外周起源厌恶特性。仔细考虑这些发现可能有助于设计新的有效药理疗法，以减少酗酒者的EtOH摄入量。

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