Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2 fever

The vasopressinergic innervation of the ventral septal area (VSA) has been shown to be implicated in antipyresis. Because this system is less well developed in female rats, we hypothesized that female rats would display exaggerated febrile responses. We therefore examined the temperature responses of conscious and urethan-anesthetized rats of both sexes to centrally administered prostaglandin E2 (PGE2) and correlated these responses with the release and action of endogenous arginine vasopressin (AVP) in the VSA. Both conscious [25 ng/5 microliters PGE2 intracerebroventricularly (i.c.v.)] and anesthetized (VSA microdialyzed, 50 ng/5 microliters PGE2 i.c.v.) female rats had higher fevers than did males. Infusion of an AVP V1a receptor antagonist {1 nmol [d(CH2)5Tyr(Me)]AVP} plus PGE2 gave rise to higher fevers in males but not in females. Measurements of AVP in microdialysates of the VSA showed that the release of endogenous AVP was increased in response to PGE2 in males only. Baseline AVP release in both sexes was similar. The results suggest that there is a sex-related difference in PGE2 fever, which may be accounted for by the differential AVP release in the VSA.