Effects of lubeluzole on the methamphetamine-induced increase in extracellular glutamate and the long-term depletion of striatal dopamine.
Effects of lubeluzole on the methamphetamine-induced increase in extracellular glutamate and the long-term depletion of striatal dopamine.
复制标题
卢贝鲁佐对甲基苯丙胺诱导的细胞外谷氨酸增加和纹状体多巴胺长期消耗的影响。
DOI：
10.1002/syn.1030
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Gudelsky,GA
中科院分区：
文献类型：
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作者：
Wallace,TL;Vorhees,CV;Gudelsky,GA
甲基苯丙胺（MA）神经毒性方案的给药导致大鼠纹状体中多巴胺和谷氨酸的细胞外浓度急性升高，以及纹状体多巴胺含量的长期耗竭。本研究的目的是确定MA诱导的细胞外谷氨酸增加的衰减是否会阻止纹状体多巴胺的消耗。雄性大鼠用MA（10 mg/kg，i. p.）或溶剂，每2小时注射一次，共注射4次，并同时用人工脑脊液或卢贝鲁唑（300 μM）进行纹状体内灌注，卢贝鲁唑是一种新型神经保护剂，已被证明可防止诱导大鼠新皮质梗死后细胞外谷氨酸的增加。卢贝鲁唑显著减弱了MA诱导的纹状体细胞外谷氨酸增加，而不影响MA诱导的细胞外多巴胺增加或MA诱导的高热反应。然而，卢贝鲁唑不能阻止MA神经毒性方案产生的纹状体多巴胺的长期消耗。这些结果表明，MA诱导的纹状体多巴胺耗竭可能不依赖于纹状体谷氨酸的细胞外浓度增加。Synapse 40：95-101，2001.© 2001 Wiley利斯公司
The administration of a neurotoxic regimen of methamphetamine (MA) produces an acute elevation in the extracellular concentrations of dopamine and glutamate in the striatum and a long‐term depletion of striatal dopamine content in rats. The intent of the present study was to determine whether attenuation of the MA‐induced increase in extracellular glutamate would prevent the depletion of striatal dopamine. Male rats were treated with MA (10 mg/kg, i.p.) or vehicle every 2 h for four injections and concomitantly perfused intrastriatally with either artificial cerebrospinal fluid or lubeluzole (300 μM), a novel neuroprotectant that has been shown to prevent the increase in extracellular glutamate after the induction of neocortical infarct in rats. Lubeluzole significantly attenuated the MA‐induced increase in extracellular glutamate in the striatum without affecting the MA‐induced increase in extracellular dopamine or the MA‐induced hyperthermic response. Nevertheless, lubeluzole did not prevent the long‐term depletion of striatal dopamine produced by a neurotoxic regimen of MA. These results suggest that the MA‐induced depletion of striatal dopamine may not be dependent on the increased extracellular concentration of striatal glutamate. Synapse 40:95–101, 2001. © 2001 Wiley‐Liss, Inc.