The recent indications that hormone-replacement therapy might improve cognitive abilities and delay the onset of Alzheimer's disease in post-menopausal women has led to increased research on neural mechanisms of action of estrogens. However, there seems to be little research on sex steroids' regulation of neuropeptides such as vasopressin (VP) in the hippocampus, despite extensive evidence these substances have numerous cognition-enhancing and neurotrophic properties and are often regulated by sex steroids. These proposals build on evidence that VP is regulated by both estrogens and androgens in the hippocampus and that intrahippocampal VP has many of the cellular and behavioral properties ascribed to sex steroids. The proposed experiments are designed to examine causal relationships and to begin determining if some of the neuroprotective and cognition-enhancing properties of gonadal steroids result from their regulation of VP in the hippocampus. These experiments seek to differentiate the influences of estrogenic and androgenic metabolites of testosterone in the male, and also examine the affects of seasonal changes in light on the sensitivity of VP cells to steroids. The results could offer clues to seasonal affective disorders and to differential responses to hormone-replacement therapy in humans.
