NMDA receptor GluN2A subunit deletion protects against dependence-like ethanol drinking.
NMDA receptor GluN2A subunit deletion protects against dependence-like ethanol drinking.
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DOI：
10.1016/j.bbr.2018.06.029
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发表时间：
2018-11-01
影响因子：
2.7
通讯作者：
Holmes A
中科院分区：
文献类型：
--
作者：
Jury NJ;Radke AK;Pati D;Kocharian A;Mishina M;Kash TL;Holmes A
N-甲基-D-天冬氨酸受体(NMDAR)在机械上参与了酒精的行为和神经生理效应，但GluN2A亚基的具体作用尚不清楚。在这里，我们将结构性GluN2A基因敲除(KO)的小鼠暴露于慢性间歇性乙醇蒸气(CIE)中，并使用两瓶选择范式测试乙醇消耗/偏好，以及通过体外切片电生理学测试NMDAR介导的杏仁基底外侧突触的传递。结果表明，GluN2AKO小鼠对CIE暴露的反应达到了相似的血液乙醇水平，但没有表现出与CIE暴露的野生型小鼠相同的乙醇饮用量显著增加。与空气暴露相比，GluN2AKO小鼠在BLA NMDAR介导的突触传递方面也没有变化，而C57BL/6J小鼠对GluN2B拮抗剂的突触反应减弱。综上所述，这些数据增加了越来越多的证据，支持含有GluN2A的NMDARs是反复接触乙醇后发生乙醇依赖的相对风险的潜在机制。
The N-methyl-D-aspartate receptor (NMDAR) is mechanistically involved in the behavioral and neurophysiological effects of alcohol, but the specific role of the GluN2A subunit remains unclear. Here, we exposed mice with constitutive GluN2A gene knockout (KO) to chronic intermittent ethanol vapor (CIE) and tested for EtOH consumption/preference using a two-bottle choice paradigm, as well as NMDAR-mediated transmission at basolateral amygdala synapses via ex vivo slice electrophysiology. Results showed that GluN2A KO mice attained comparable blood EtOH levels in response to CIE exposure, but did not exhibit the significant increase in EtOH drinking that was observed in CIE-exposed wildtypes. GluN2A KO mice also showed no alterations in BLA NMDAR-mediated synaptic transmission after CIE, relative to air-exposed, whereas C57BL/6 J mice showed an attenuated synaptic response to GluN2B antagonism. Taken together, these data add to mounting evidence supporting GluN2A-containing NMDARs as a mechanism underlying relative risk for developing EtOH dependence after repeated EtOH exposure.
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DOI：
10.1523/jneurosci.5017-09.2010
发表时间：
2010-04-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Mozhui K;Karlsson RM;Kash TL;Ihne J;Norcross M;Patel S;Farrell MR;Hill EE;Graybeal C;Martin KP;Camp M;Fitzgerald PJ;Ciobanu DC;Sprengel R;Mishina M;Wellman CL;Winder DG;Williams RW;Holmes A
通讯作者：
Holmes A
影响因子：
4.5
作者：
Lo CL;Lossie AC;Liang T;Liu Y;Xuei X;Lumeng L;Zhou FC;Muir WM
通讯作者：
Muir WM
DOI：
10.1038/npp.2009.69
发表时间：
2009-10
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Bach, Patrick;Kirsch, Martina;Vollstaedt-Klein, Sabine
通讯作者：
Vollstaedt-Klein, Sabine
影响因子：
5.3
作者：
Abrahao, Karina Possa;Ariwodola, Olusegun J.;Weiner, Jeffrey L.
通讯作者：
Weiner, Jeffrey L.