Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE(2) 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 E-2 (PGE(2)) and correlated these responses with the release and action of endogenous arginine vasopressin (AVP) in the VSA. Both conscious [25 ng/5 mu l PGE(2) intracerebroventricularly (icv)] and anesthetized (VSA microdialyzed, 50 ng/5 mu l PGE(2) icv) female rats had higher fevers than did males. Infusion of an AVP V-1a receptor antagonist [1 nmol [d(CH2)(5)Tyr(Me)]AVP] plus PGE(2) 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 PGE(2) in males only. Baseline AVP release in both sexes was similar. The results suggest that there is a sex-related difference in PGE(2) fever, which may be accounted for by the differential AVP release in the VSA.