Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport.
Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport.
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DOI：
10.3389/fphar.2015.00027
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发表时间：
2015
影响因子：
5.6
通讯作者：
Becker HC
中科院分区：
文献类型：
--
作者：
Griffin WC;Ramachandra VS;Knackstedt LA;Becker HC
慢性间歇性乙醇(CIE)暴露的反复循环增加了小鼠对乙醇的自愿消费。以往的工作表明，在酒精依赖的小鼠中，伏隔核(NAC)中的细胞外谷氨酸显著升高，药理上控制NAC中的谷氨酸浓度将改变饮酒行为，表明谷氨酸稳态在该模型中饮酒中起着至关重要的作用。目前的研究旨在测量在CIE模型中通常允许小鼠自愿获得乙醇的时间点的细胞外谷氨酸，并在同一时间点测量NAC中谷氨酸的转运能力。用定量微透析法测定细胞外谷氨酸。在Na+依赖和非Na+依赖条件下测定谷氨酸转运能力，以确定兴奋性氨基酸转运体(也称为XAG系统)或XC-(胶质半胱氨酸-谷氨酸交换)系统的功能是否受到CIE暴露的影响。定量微透析实验的结果证实，与NAC中的非依赖小鼠相比，CIE暴露(即酒精依赖)的小鼠NAC中细胞外谷氨酸增加(约两倍)，这与早期的工作一致。然而，细胞外谷氨酸的增加并不是由于酒精依赖小鼠NAC中转运蛋白功能的改变，因为CIE暴露对Na+依赖和Na+非依赖性谷氨酸运输都没有显著改变。这些发现表明，皮层-纹状体通路的过度兴奋性可能是酒精依赖小鼠细胞外谷氨酸增加的基础。
Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+-dependent and Na+-independent conditions to determine whether the function of excitatory amino acid transporters (also known as system XAG) or of system Xc– (glial cysteine–glutamate exchanger) was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent) compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+-dependent nor Na+-independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical–striatal pathways underlies the increases in extracellular glutamate found in the ethanol-dependent mice.
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DOI：
10.1111/j.1601-183x.2010.00647.x
发表时间：
2011-02
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Goulding SP;Obara I;Lominac KD;Gould AT;Miller BW;Klugmann M;Szumlinski KK
通讯作者：
Szumlinski KK
影响因子：
3.4
作者：
Chefer V;Meis J;Wang G;Kuzmin A;Bakalkin G;Shippenberg T
通讯作者：
Shippenberg T
影响因子：
3.4
作者：
Griffin, William C., III;Lopez, Marcelo F.;Yanke, Amy B.;Middaugh, Lawrence D.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
7.6
作者：
Griffin, William C., III;Haun, Harold L.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
7.6
作者：
Abulseoud, Osama A.;Camsari, Ulas M.;Choi, Doo-Sup
通讯作者：
Choi, Doo-Sup