Central effects of acamprosate:: Part 1.: Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats
Central effects of acamprosate:: Part 1.: Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats
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DOI：
10.1016/s0925-4927(98)00016-x
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发表时间：
1998-05-20
影响因子：
2.3
通讯作者：
Macher, JP
中科院分区：
文献类型：
--
作者：
Dahchour, A;De Witte, P;Macher, JP
阿坎酸的已知行为作用之一是减少戒酒期间的过度运动。然而，这种效应的机制仍不清楚。本研究采用 OPA/BME 柱前衍生化和电化学检测的微透析技术测定了雄性 Wistar 大鼠的伏核中兴奋性和抑制性氨基酸的浓度，这些大鼠通过乙醇吸入酒精或同时酒精并口服阿坎酸（400 mg/kg/天）治疗 4 周。如果不进行治疗，细胞外谷氨酸在戒断阶段会增加，而其他测试的氨基酸（天冬氨酸、精氨酸、牛磺酸、丙氨酸和 GABA）保持稳定。相比之下，用阿坎酸治疗的酗酒大鼠在乙醇戒断期间未能表现出谷氨酸的增加，而测试的其他氨基酸也保持稳定。观察到的谷氨酸盐增加可能是乙醇戒断期间观察到的过度兴奋的原因。这些结果表明阿坎酸能够通过降低伏核中谷氨酸的浓度来减轻乙醇戒断综合征。 (C) 1998 Elsevier Science Ireland Ltd. 保留所有权利。
One of the known behavioral actions of acamprosate is to decrease hypermotility during alcohol withdrawal. However, the mechanism of this effect remains unclear. In this study, the concentrations of excitatory and inhibitory amino acids were assayed by the microdialysis technique with OPA/BME precolumn derivatization and electrochemical detection in the nucleus accumbens of male Wistar rats which were either alcoholized by ethanol inhalation or simultaneously alcoholized and treated orally by acamprosate (400 mg/kg/day) for 4 weeks. Without treatment, extracellular glutamate increased during the withdrawal phase, while other amino acids tested (aspartate, arginine, taurine, alanine and GABA) remained stable. In contrast, the alcoholized rats treated with acamprosate failed to present the increase in glutamate during ethanol withdrawal, while other amino acids tested also remained stable. The observed glutamate increase could be responsible for the hyperexcitability observed during episodes of ethanol withdrawal. These results suggest that acamprosate is able to reduce the ethanol withdrawal syndrome by reducing the concentration of glutamate in the nucleus accumbens. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.