Jury Nicholas J, Radke Anna K, Pati Dipanwita, Kocharian Adrina, Mishina Masayoshi, Kash Thomas L, Holmes Andrew
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Behav Brain Res. 2018 Nov 1;353:124-128. doi: 10.1016/j.bbr.2018.06.029. Epub 2018 Jun 25.
The N-methyl--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.
N-甲基-D-天冬氨酸受体（NMDAR）在酒精的行为和神经生理效应中发挥作用，但其GluN2A亚基的具体作用尚不清楚。在此，我们将组成型GluN2A基因敲除（KO）小鼠暴露于慢性间歇性乙醇蒸汽（CIE）中，并使用双瓶选择范式测试其乙醇消耗/偏好，同时通过离体脑片电生理学检测基底外侧杏仁核突触处NMDAR介导的传递。结果显示，GluN2A基因敲除小鼠在暴露于CIE后达到了与野生型相当的血液乙醇水平，但并未表现出暴露于CIE的野生型小鼠中观察到的乙醇摄入量显著增加。相对于暴露于空气的小鼠，CIE处理后的GluN2A基因敲除小鼠在基底外侧杏仁核中NMDAR介导的突触传递也未出现改变，而C57BL/6J小鼠对GluN2B拮抗剂的突触反应减弱。综上所述，这些数据进一步证明了含GluN2A的NMDAR是反复暴露于乙醇后发生乙醇依赖相对风险的潜在机制。
