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Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit

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Abstract

Rationale

The ionotropic NMDA glutamate receptor is composed of NR1 and NR2 (NR2A-D) subunits. While there is compelling evidence that NMDA receptors modulate behavioral effects of ethanol, there is little understanding of how the subunit composition of the NMDA receptor mediates these effects.

Objectives

In the current study, we assessed the relative roles of NMDA subunits via phenotypic assessment of ethanol-related behaviors in NR2A knockout (KO) mice.

Results

Results demonstrated that NR2A KO and heterozygous mice failed to show evidence of ethanol-induced conditioned place preference. As compared to wild-type (WT) controls, KO mice showed impaired motor coordination at baseline and, in some instances, following ethanol treatment on the accelerating rotarod, balance beam, and wire-hang tests. By contrast, open field locomotor-stimulant, sedative/hypnotic, and hypothermic responses to ethanol were not different between genotypes, nor was voluntary ethanol consumption and preference in a two-bottle choice paradigm. Blood ethanol concentrations were lower in KO than WT mice following intraperitoneal ethanol injection.

Conclusions

Results suggest that the loss of NR2A subunit-containing NMDA receptors impairs the ability to form or express learned reward-related responses to ethanol and causes deficits in motor coordination. However, the loss of NR2A does not alter other measures of acute ethanol intoxication or ethanol consumption, possibly implicating other NMDA subunits in these effects. These data provide novel insight into the role of NMDA receptors in modulating the behavioral effects of ethanol.

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Acknowledgements

We thank Dr. Masayoshi Mishina for providing the breeding stocks used for these studies, Dr. David Lovinger for helpful comments on an earlier version of the manuscript. Research was supported by the National Institute on Alcohol Abuse and Alcoholism Research Program.

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Authors and Affiliations

  1. Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, 20852, USA

    Janel M. Boyce-Rustay & Andrew Holmes

  2. Abbott Laboratories, R4CY 13A-2, 100 Abbott Park Rd, Abbott Park, IL, 60064-6126, USA

    Janel M. Boyce-Rustay

Authors
  1. Janel M. Boyce-Rustay
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  2. Andrew Holmes
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Correspondence to Janel M. Boyce-Rustay.

Additional information

Research supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program.

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Boyce-Rustay, J.M., Holmes, A. Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit. Psychopharmacology 187, 455–466 (2006). https://doi.org/10.1007/s00213-006-0448-6

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  • DOI: https://doi.org/10.1007/s00213-006-0448-6

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