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.