Ethanol Increases Glutamate Neurotransmission in the Posterior Ventral Tegmental Area of Female Wistar Rats
Ethanol Increases Glutamate Neurotransmission in the Posterior Ventral Tegmental Area of Female Wistar Rats
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DOI：
10.1111/j.1530-0277.2011.01665.x
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发表时间：
2012-04-01
影响因子：
3.2
通讯作者：
McBride, William J.
中科院分区：
文献类型：
--
作者：
Ding, Zheng-Ming;Engleman, Eric A.;McBride, William J.
背景：后腹侧被盖区（pVTA）介导乙醇（EtOH）的强化和刺激作用。电生理学研究表明，暴露于乙醇增加谷氨酸突触功能的腹侧被盖区。本研究确定了急性和反复乙醇暴露对谷氨酸神经传递的pVTA.Methods：成年雌性Wistar大鼠植入微透析探针在pVTA的神经化学作用。在微透析期间，大鼠接受急性腹膜内（i. p.）注射盐水或EtOH（0.5、1.0或2.0 g/kg），并在pVTA中测量细胞外谷氨酸水平。每天重复注射乙醇的效果还检查了（0.5、1.0或2.0 g/kg）对pVTA中基础细胞外谷氨酸浓度和对随后EtOH攻击的谷氨酸响应的影响。注射0.5g/kg乙醇显著增加（基线的120至125%），而注射2.0 g/kg EtOH显着降低了pVTA中细胞外谷氨酸水平（基线的80%）。1.0 g/kg EtOH剂量未改变细胞外谷氨酸水平。每天重复注射七次，每次剂量的EtOH增加基础细胞外谷氨酸浓度（从4.1 +/- 0.5至9.2 +/- 0.5 μ M）和pVTA中谷氨酸清除率降低（从30 +/-2%到17 +/- 2%），但未能改变谷氨酸对2.0 g/kg EtOH挑战的反应。结果表明，低剂量的EtOH可以刺激pVTA中谷氨酸的释放，并且重复的EtOH给药增加了pVTA中的基础谷氨酸传输，这是由于谷氨酸清除率降低。
Background: The posterior ventral tegmental area (pVTA) mediates the reinforcing and stimulating effects of ethanol (EtOH). Electrophysiological studies indicated that exposure to EtOH increased glutamate synaptic function in the VTA. This study determined the neurochemical effects of both acute and repeated EtOH exposure on glutamate neurotransmission in the pVTA.Methods: Adult female Wistar rats were implanted with microdialysis probes in the pVTA. During microdialysis, rats received acute intraperitoneal (i.p.) injection of saline or EtOH (0.5, 1.0, or 2.0 g/kg), and extracellular glutamate levels were measured in the pVTA. The effects of repeated daily injections of EtOH (0.5, 1.0, or 2.0 g/kg) on basal extracellular glutamate concentrations in the pVTA and on glutamate response to a subsequent EtOH challenge were also examined.Results: The injection of 0.5 g/kg EtOH significantly increased (120 to 125% of baseline), whereas injection of 2.0 g/kg EtOH significantly decreased (80% of baseline) extracellular glutamate levels in the pVTA. The dose of 1.0 g/kg EtOH did not alter extracellular glutamate levels. Seven repeated daily injections of each dose of EtOH increased basal extracellular glutamate concentrations (from 4.1 +/- 0.5 to 9.2 +/- 0.5 mu M) and reduced glutamate clearance in the pVTA (from 30 +/- 2 to 17 +/- 2%), but failed to alter glutamate response to a 2.0 g/kg EtOH challenge.Conclusions: The results suggest that the low dose of EtOH can stimulate the release of glutamate in the pVTA, and repeated EtOH administration increased basal glutamate transmission in the pVTA, as a result of reduced glutamate clearance.