Toll-like receptor 3 neuroimmune signaling and behavior change: A strain comparison between Lewis and Wistar rats

There are many unanswered questions about the interaction between the immune system and behavior change, including the contributions of individual differences. The present study modeled individual differences in the immune system by comparing inbred Lewis rats, which have dysregulated stress and immune systems, to their genetically diverse parent strain, Wistar rats. The objective was to examine the consequences of an immune challenge on behavior and neuroimmune signaling in both strains. Peripheral administration of the toll-like receptor 3 (TLR3) agonist and viral memetic polyinosinic-polycytidylic acid (poly(I:C)) induced behavior changes in both strains, reducing locomotor activity and increasing avoidance behavior (time on the dark side of the light-dark box). Furthermore, poly(I:C) induced hyperarousal and increased avoidance behavior more in female Lewis than female Wistar rats. Baseline strain differences were also observed: Lewis rats had higher avoidance behavior and lower startle response than Wistars. Lewis rats also had lower levels of peripheral inflammation, as measured by spleen weight. Finally, poly(I:C) increased expression of genes in the TLR3 pathway, cytokine genes, and CD11b, a gene associated with proinflammatory actions of microglia, in the prelimbic cortex and central amygdala, with greater expression of cytokine genes in male rats. Lewis rats had lower baseline expression of some neuroimmune genes, particularly CD11b. Overall, we found constitutive strain differences in immune profiles and baseline differences in behavior, yet poly(I:C) generally induced similar behavior changes in males while hyperarousal and avoidance behavior were heightened in female Lewis rats.