Central vasopressin V1-receptors mediate indomethacin-induced antipyresis in rats

Central microinjection or infusion of an arginine vasopressin (AVP) V1-receptor antagonist within the brain of the conscious, unrestrained, and febrile rat inhibited or abolished the antipyretic effects of peripherally administered indomethacin (Indo). The degree of Indo-induced antipyresis was determined by 2-h thermal indexes (degree C.h) calculated from the time of Indo injection. Microinjection of saline or V1-receptor antagonist within the ventral septal area (VSA) of the rat brain immediately followed by intraperitoneal Indo evoked antipyretic responses of -1.63 +/- 0.17 and -0.24 +/- 0.09 degrees C.h, respectively (P less than 0.01). Infusion of the VSA with saline or V1-receptor antagonist before and after Indo resulted in thermal indexes of -1.35 +/- 0.16 and 0.13 +/- 0.30 degree C.h, respectively (P less than 0.01). Central microinjection of a V2-receptor antagonist did not significantly effect Indo-induced antipyresis compared with paired saline controls. Neither saline nor the V1-receptor antagonist affected nonfebrile body temperature when microinjected into the VSA. These data indicate the importance of AVP V1-receptors within the VSA in mediating the potent fever-reducing properties of the antipyretic drug Indo. Furthermore, these data call into question whether prostaglandin synthesis inhibition is a sufficient explanation of drug-induced antipyresis.