Dexmedetomidine prevents high mobility group box 1 protein (HMGB1)–induced hippocampal inflammation in an atipamezole- and methyllycaconitine-sensitive manner. Ten groups of randomly assigned mice (n = 8/group) were administered antagonists (methyllycaconitine, atipamezole, yohimbine) before HMGB1 in the presence or absence of dexmedetomidine. Twenty-four hours after HMGB1, mice were euthanized, and the hippocampus was harvested and assayed by ELISA for interleukin (IL)-1β (A) and IL-6 (B). Data are expressed as means ± SD and were analyzed by one-way ANOVA and Tukey post hoc test. *P < 0.0001 for comparisons shown.