Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP 1 and EP 3 receptors

Previous studies have disagreed about whether prostaglandin EP 1 or EP 3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 μg kg −1 ‐1 mg kg −1 ) intraperitoneally (I.P.) into wild‐type (WT) mice and mice lacking the EP 1 or the EP 3 receptors and measured changes in core temperature ( T c ) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg −1 increased T c about 1 °C, peaking 2 h after injection. At 100 μg kg −1 , LPS increased T c , peaking 5‐8 h after injection. LPS at 1 mg kg −1 decreased T c , reaching a nadir at 5‐8 h after injection. In EP 1 receptor knockout (KO) mice injected with 10 μg kg −1 LPS, only the initial (< 40 min) increase in T c was lacking; with 100 μg kg −1 LPS the mice showed no febrile response. In EP 3 receptor KO mice, LPS decreased T c in a dose‐ and time‐dependent manner. Furthermore, in EP 3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP 1 and EP 3 receptor KO mice showed a normal circadian cycle of T c and brief hyperthermia following psychological stress (cage‐exchange stress and buddy‐removal stress). The present study suggests that both the EP 1 and the EP 3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in T c or psychological stress‐induced hyperthermia in mice.