NMDA receptor GluN2A subunit deletion protects against dependence-like ethanol drinking

Behav Brain Res. 2018 Nov 1;353:124-128. doi: 10.1016/j.bbr.2018.06.029. Epub 2018 Jun 25.


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.

Keywords: Addiction; Alcohol; Amygdala; CIE; Glutamate; NMDA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / metabolism
  • Alcoholism / metabolism*
  • Animals
  • Basolateral Nuclear Complex / drug effects
  • Basolateral Nuclear Complex / metabolism
  • Central Nervous System Depressants / administration & dosage
  • Choice Behavior / physiology
  • Ethanol / administration & dosage
  • Female
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / metabolism
  • Phenols / pharmacology
  • Piperidines / pharmacology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / deficiency*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tissue Culture Techniques


  • Central Nervous System Depressants
  • Phenols
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Ro 25-6981
  • Ethanol
  • N-methyl D-aspartate receptor subtype 2A