Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory.
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.
Department of Neuroscience, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, United States.
Ja Wook
JW
Koo
Ronald S
RS
Duman
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant; D005239:Fear / Q000502:physiology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D010146:Pain / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I