PKCε-/- mice show enhanced tolerance to WIN55,212-2-induced hypothermia and analgesia following equipotent, twice daily injections of WIN55,212-2 for 6 days. (a) PKCε-/- mice showed tolerance to WIN55,212-2 induced hypothermia (*p< 0.001 by Bonferroni post-hoc test). (b) PKCε+/+ mice also showed tolerance to WIN55,212-2-induced hypothermia (*p< 0.001 by Bonferroni post-hoc test). (c) The magnitude of tolerance to WIN55,212-2-induced hypothermia was greater in PKCε-/- compared with PKCε+/+ mice. (d) PKCε-/- mice showed tolerance to WIN55,212-2-induced analgesia (*p<0.05 by Bonferroni post-hoc test). (e) PKCε+/+ mice did not show significant tolerance to WIN55,212-2-induced analgesia. (f) The magnitude of chronic tolerance to WIN55,212-2 induced analgesia was greater in PKCε-/- compared with PKCε+/+ mice (*p< 0.05 by Bonferroni post-hoc test). Data represent mean ± standard error of 5 to 9 mice per genotype.