Fig. 3.
AMG 517 prevents ketamine-induced hypothermia by increasing thermogenesis. (A) In unanesthetized rats (received saline intraperitoneally; i.p.), AMG 517 (1 mg/kg intravenously; i.v.) was injected, and changes in core body temperature, tail skin temperature, and oxygen consumption (Vo2) were measured. AMG 517 resulted in a statistically significant rise in core body temperature immediately after injection that lasted until the last measurement of 240 min (top graph). AMG 517 did not result in any significant change in tail skin temperature (middle graph) but significantly increased oxygen consumption (bottom graph) that was statistically significant from 30 to 190 min compared with the controls (n = 11 for vehicle; n = 6 for AMG 517; *P < 0.05, two way ANOVA with Bonferroni post hoc test, error bars = SD). (B) In anesthetized rats (ketamine 100 mg/mg i.p.), AMG 517 (1 mg/kg iv) reversed ketamine-induced hypothermia (top graph) and transiently increased tail skin temperature (only until 40 min postinjection; middle graph). Ketamine (100 mg/kg) initially (20 to 100 min) decreased oxygen consumption (Vo2; bottom graph) that was not observed in AMG 517–treated animals. Moreover, in AMG 517–treated animals, Vo2 remained significantly higher at most time points (40 min onwards) compared with vehicle-treated animals (n = 6 vehicle; n = 5 AMG; *P < 0.05, two-way ANOVA with Bonferroni post hoc test, ANOVA showed that the effect of AMG 517 on oxygen consumption was significant, F(1, 9) = 11.083; P < 0.001; error bars = SD).