Ethanol exposure decreases glutamate uptake in the nucleus accumbens
Ethanol exposure decreases glutamate uptake in the nucleus accumbens
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DOI：
10.1097/01.alc.0000156086.65665.4d
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发表时间：
2005-03-01
影响因子：
3.2
通讯作者：
Kalivas, PW
中科院分区：
文献类型：
--
作者：
Melendez, RI;Hicks, MP;Kalivas, PW
背景资料：细胞外谷氨酸水平的增加是与乙醇暴露和戒断相关的一个关键神经化学特征。方法：在本研究中，重复乙醇暴露24小时后，测定细胞外谷氨酸水平和延髓核谷氨酸转运（每天ip 1g/kg，持续7天），分别使用体内无净通量微透析和体外[H-3]谷氨酸摄取。微透析显示，给予乙醇的大鼠的脑桥核中细胞外谷氨酸浓度较高。基础细胞外谷氨酸水平的增加部分是由于体内谷氨酸探针回收率的降低。此外，在体外测量[H-3]谷氨酸盐摄取的Spanbens切片制备显示，Na+依赖的[H-3]谷氨酸盐摄取显着减少24小时后，7天的重复乙醇暴露。乙醇诱导的谷氨酸吸收缺陷与转运蛋白GLAST或GLT 1的总组织水平下降无关。在体内和体外乙醇诱导的谷氨酸水平和摄取的变化恢复到控制水平14天后，停止7天的重复乙醇exposure.Conclusions：这些结果表明，先前报道的乙醇暴露引起的细胞外谷氨酸的增加可能是由于部分赤字谷氨酸转运。
Background: An increased level of extracellular glutamate is a key neurochemical feature associated with ethanol exposure and withdrawal.Methods: In the current study, extracellular levels of glutamate and glutamate transport in the nucleus accumbens were assayed 24 hr after repeated ethanol exposure (1 g/kg ip daily for 7 days) with use of in vivo no-net-flux microdialysis and in vitro [H-3]glutamate uptake, respectively.Results: Microdialysis revealed higher extracellular glutamate concentrations in the nucleus accumbens of rats that were given ethanol. The increase in basal extracellular glutamate levels was accounted for in part by a decrease in the in vivo probe recovery of glutamate. Moreover, an in vitro accumbens slice preparation measuring [H-3]glutamate uptake revealed that Na+-dependent [H-3]glutamate uptake was significantly reduced 24 hr after 7 days of repeated ethanol exposure. The ethanol-induced deficit in glutamate uptake was not associated with decreased total tissue levels of the transporters GLAST or GLT1. The in vivo and in vitro ethanol-induced changes in glutamate levels and uptake returned to control levels 14 days after discontinuing 7 days of repeated ethanol exposure.Conclusions: These results suggest that the previously reported increases in extracellular glutamate induced by ethanol exposure may be due in part to deficits in glutamate transport.