Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Neurobiol Aging. 2014 May;35(5):1213.e3-8. doi: 10.1016/j.neurobiolaging.2013.11.014. Epub 2013 Nov 22.


Both the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20-31 years; n = 670) and older (59-71 years; n = 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

Keywords: Aging; D2 receptors; Dopamine; Episodic memory; Gene-gene interactions; Glutamate; NMDA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / genetics*
  • Aging / psychology*
  • Dopamine / physiology
  • Epistasis, Genetic / physiology*
  • Female
  • Genetic Variation*
  • Genotype
  • Glutamic Acid / physiology
  • Humans
  • Male
  • Memory, Episodic*
  • Middle Aged
  • Neurotransmitter Agents / physiology
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D2 / physiology*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Young Adult


  • NR3A NMDA receptor
  • Neurotransmitter Agents
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dopamine