Hippocampal GluR1 associates with behavior in the elevated plus maze and shows sex differences

Behav Brain Res. 2011 Sep 23;222(2):326-31. doi: 10.1016/j.bbr.2011.03.068. Epub 2011 Apr 7.


The hippocampus is involved in anxiety as well as spatial memory formation and is sexually dimorphic. Female rats typically show less anxiety in elevated plus maze procedure (EPM), a standard animal model of anxiety. Many intracellular proteins, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 and the cyclic AMP response element-binding protein (CREB), in hippocampus contribute to memory formation. However, less is known about the roles for hippocampal GluR1 and CREB in anxiety. We examined behavior in EPM in male and female rats and obtained hippocampal tissue samples to determine levels of GluR1 and CREB with western blots. EPM results showed that female rats exhibited less anxiety-like behaviors than male rats. Further, behaviors in EPM were significantly correlated with hippocampal GluR1 levels, but not with CREB. Yet, both proteins showed sex differences with lower levels in female rats. These data not only suggest some potential bases for sex differences in behaviors to which the hippocampus contributes but demonstrate that there is a strong association between hippocampal GluR1 levels and anxiety as assessed with EPM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disease Models, Animal
  • Female
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Male
  • Maze Learning / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology*
  • Sex Characteristics*


  • Cyclic AMP Response Element-Binding Protein
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 1