Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory

Neurosci Lett. 2009 May 29;456(1):39-43. doi: 10.1016/j.neulet.2009.03.068. Epub 2009 Mar 27.


IL-1beta is a proinflammatory cytokine that contributes to psychological stress responses and has been implicated in various psychiatric disorders most notably depression. Preclinical studies also demonstrate that IL-1beta modulates anxiety- and fear-related behaviors, although these findings are difficult to assess because IL-1beta infusions influence locomotor activity and nociception. Here we demonstrate that IL-1RI null mice exhibit a behavioral phenotype consistent with a decrease in anxiety-related behaviors. This includes significant effects in the elevated plus maze, light-dark, and novelty-induced hypophagia tests compared to wild-type mice, with no differences in locomotor activity. With regard to fear conditioning, IL-1RI null mice showed more freezing in auditory and contextual fear conditioning tests, and there was no effect on pain sensitivity. Taken together, the results indicate that the IL-1beta/IL-1RI signaling pathway induces anxiety-related behaviors and impairs fear memory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Conditioning, Operant
  • Fear / physiology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Male
  • Maze Learning / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Pain / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 Type I / deficiency
  • Receptors, Interleukin-1 Type I / genetics*
  • Signal Transduction / genetics


  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I