Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release.
Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release.
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DOI：
10.1111/j.1369-1600.2010.00272.x
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Shippenberg T
中科院分区：
文献类型：
--
作者：
Chefer V;Meis J;Wang G;Kuzmin A;Bakalkin G;Shippenberg T
本研究采用常规和定量微透析法研究中等剂量乙醇处理后大鼠海马CA3区谷氨酸和氨基丁酸能神经传递的变化。雄性Wistar大鼠以3.4g/kg乙醇或水灌胃6d。2天后开始微透析实验。在酒精处理的动物中，基础和去极化引起的谷氨酸溢出显著增加。基础和去极化诱导的γ-氨基丁酸(GABA)溢出未见改变。定量无净通量微透析法被用来确定乙醇注射后透析液谷氨酸水平的变化是由于谷氨酸释放的增加还是摄取的减少。为了证实这种方法在定量基础谷氨酸动态方面的有效性，对谷氨酸摄取阻滞剂反式吡咯烷-2，4-二元酸(TPDC)反透析的反应，定量了细胞外谷氨酸浓度和反映分析物清除量变化的提取分数。TPDC显著降低了谷氨酸的萃取率，导致胞外谷氨酸浓度升高。反复给予乙醇并没有改变谷氨酸的提取分数。然而，胞外谷氨酸浓度显著升高，这表明反复给予乙醇会增加谷氨酸的释放。这些数据表明，反复适度饮酒改变了背侧海马区CA3区的基础谷氨酸动态。基础谷氨酸释放增加，而谷氨酸摄取没有变化。此外，他们还提出，该区域谷氨酸传递的失调可能是先前证明的与中等剂量乙醇使用有关的认知功能缺陷的原因之一。
The present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate-dose ethanol treatment regimen. Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization-induced glutamate overflow were significantly elevated in ethanol-treated animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow were unaltered. Quantitative no-net-flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake.To confirm the validity of this method for quantifying basal glutamate dynamics, extracellular concentrations of glutamate and the extraction fraction, which reflects changes in analyte clearance, were quantified in response to retro-dialysis of the glutamate uptake blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly decreased the extraction fraction for glutamate, resulting in augmented extracellular glutamate concentrations. Repeated ethanol administration did not alter the glutamate extraction fraction. However, extracellular glutamate concentrations were significantly elevated, indicating that glutamate release is increased as a consequence of repeated ethanol administration. These data demonstrate that repeated bouts of moderate ethanol consumption alter basal glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate release is augmented, whereas glutamate uptake is unchanged. Furthermore, they suggest that dysregulation of glutamate transmission in this region may contribute to the previously documented deficits in cognitive function associated with moderate dose ethanol use.
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影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
DOI：
10.1097/01.alc.0000156086.65665.4d
发表时间：
2005-03-01
影响因子：
3.2
作者：
Melendez, RI;Hicks, MP;Kalivas, PW
通讯作者：
Kalivas, PW
DOI：
10.1097/01.alc.0000171038.03371.56
发表时间：
2005-06-01
影响因子：
3.2
作者：
Farr, SA;Scherrer, JF;Morley, JE
通讯作者：
Morley, JE
影响因子：
56.9
作者：
LOVINGER, DM;WHITE, G;WEIGHT, FF
通讯作者：
WEIGHT, FF
DOI：
10.1111/j.1530-0277.1996.tb01641.x
发表时间：
1996-04-01
影响因子：
3.2
作者：
Collins, MA;Corso, TD;Neafsey, EJ
通讯作者：
Neafsey, EJ