(A) Experimental paradigm. Wild type (WT) and RAGE deletion mutant mice were tested for (B) sucrose consumption (main effect of stress F(1,33)=11.39, p=0.0019; no interaction of stress and genotype) and (C) water consumption (no effect F(1,33)=0.0806, p=0.7783 ). Mice were tested for (D) novel object recognition 24h after familiar object exposure (interaction of stress and genotype F(1,15)=4.853, p=0.0437). (E) Total cage locomotor activity within a 20 min period (no effect F(1,30)=0.1782, p=0.6759). The results are expressed as the mean ± SEM. N=6–10 animals per group. (F) Experimental paradigm for disulfide HMGB1 (dsHMGB1) infusion in naïve C57BL6 mice. (G) Mice were tested for sucrose preference 4 hrs post dsHMGB1 ICV infusion (t(24)=4.399, p=0.0002). The results are expressed as the mean ± SEM. N=12–14 animals per group. *p<0.05 and ***p<0.001. Two-way ANOVA was performed followed by Bonferroni post hoc test for behavioral analysis in RAGE KO mice. Student t-test was performed for sucrose preference test following dsHMGB1 infusion.