Selective effects of peripheral lipopolysaccharide administration on contextual and auditory-cue fear conditioning

Brain Behav Immun. 1998 Sep;12(3):212-29. doi: 10.1006/brbi.1998.0524.


The reported experiments explore the effects of peripheral LPS administration on learning and memory processes. As measured by the conditioned freezing response, intraperitoneal LPS administration given after conditioning impaired contextual but not auditory-cue fear conditioning in both juvenile (hooded Long Evans) and adult rats (albino Sprague Dawley) of two different strains. This impairment in contextual fear conditioning was not dependent on the presence of the tone. Preexposure to the context eliminated the effect of LPS on contextual fear conditioning, and in addition, LPS given after context preexposure negated the beneficial effects of preexposure on contextual fear. These results suggest that LPS disrupts posttrial memory consolidation processes. In support of the hypothesis that LPS-induced proinflammatory cytokine release is involved in producing the impairment in contextual fear caused by LPS, peripheral interleukin-1 receptor antagonist (IL-1ra) administered subcutaneously at a dose of 100 mg/kg prevented the impairment in contextual fear caused by LPS. These experiments provide evidence for a role of immune activation and cytokine activity in learning and memory processes.

Publication types

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

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Electroshock
  • Fear*
  • Female
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Neuroimmunomodulation / physiology*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / pharmacology


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Recombinant Proteins
  • Sialoglycoproteins